Chronic hypertension increases aortic endothelial hydraulic conductivity by upregulating endothelial aquaporin-1 expression
Numerous studies have examined the role of aquaporins in osmotic water transport in various systems, but virtually none have focused on the role of aquaporin in hydrostatically driven water transport involving mammalian cells save for our laboratory’s recent study of aortic endothelial cells. Here, we investigated aquaporin-1 expression and function in the aortic endothelium in two high-renin rat models of hypertension, the spontaneously hypertensive genetically altered Wistar-Kyoto rat variant and Sprague-Dawley rats made hypertensive by two-kidney, one-clip Goldblatt surgery. We measured aquaporin-1 expression in a...
Source: AJP: Heart and Circulatory Physiology - November 6, 2017 Category: Cardiology Authors: Toussaint, J., Raval, C. B., Nguyen, T., Fadaifard, H., Joshi, S., Wolberg, G., Quarfordt, S., Jan, K.-m., Rumschitzki, D. S. Tags: RESEARCH ARTICLE Source Type: research

Exercise of obese mice induces cardioprotection and oxygen sparing in hearts exposed to high-fat load
This study therefore shows that exercise-induced cardioprotective effects are present under hyperlipidemic conditions and highlights the important role of myocardial energetics during ischemic stress. NEW & NOTEWORTHY The exercise-induced cardioprotective effects in obese hearts are present under hyperlipidemic conditions, comparable to circulating levels of FA occurring with an ischemic insult. Myocardial oxygen sparing is associated with this effect, despite the general notion that high fat can decrease cardiac efficiency. This highlights the role of myocardial energetics during ischemic stress. (Source: AJP: Heart a...
Source: AJP: Heart and Circulatory Physiology - November 6, 2017 Category: Cardiology Authors: Boardman, N. T., Hafstad, A. D., Lund, J., Rossvoll, L., Aasum, E. Tags: RESEARCH ARTICLE Source Type: research

Plastics and cardiovascular health: phthalates may disrupt heart rate variability and cardiovascular reactivity
This study also highlights the importance of adopting safer biomaterials, chemicals, and/or surface coatings for use in medical devices. NEW & NOTEWORTHY Phthalates are widely used in the manufacturing of consumer and medical products. In the present study, di-2-ethylhexyl-phthalate exposure was associated with alterations in heart rate variability and cardiovascular reactivity. This highlights the importance of investigating the impact of phthalates on health and identifying suitable alternatives for medical device manufacturing. (Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - November 6, 2017 Category: Cardiology Authors: Jaimes, R., Swiercz, A., Sherman, M., Muselimyan, N., Marvar, P. J., Posnack, N. G. Tags: RESEARCH ARTICLE Source Type: research

Effect of ovariectomy on intracellular Ca2+ regulation in guinea pig cardiomyocytes
This study addressed the hypothesis that long-term deficiency of ovarian hormones after ovariectomy (OVx) alters cellular Ca2+-handling mechanisms in the heart, resulting in the formation of a proarrhythmic substrate. It also tested whether estrogen supplementation to OVx animals reverses any alterations to cardiac Ca2+ handling and rescues proarrhythmic behavior. OVx or sham operations were performed on female guinea pigs using appropriate anesthetic and analgesic regimes. Pellets containing 17β-estradiol (1 mg, 60-day release) were placed subcutaneously in selected OVx animals (OVx + E). Cardiac myocytes were enzyma...
Source: AJP: Heart and Circulatory Physiology - November 6, 2017 Category: Cardiology Authors: Yang, H.-Y., Firth, J. M., Francis, A. J., Alvarez-Laviada, A., MacLeod, K. T. Tags: RESEARCH ARTICLE Source Type: research

Moderate-to-severe obstructive sleep apnea is associated with telomere lengthening
In conclusion, moderate-to-severe OSA is associated with telomere lengthening. Our findings support the idea that changes in TL are not unidirectional processes, such that telomere shortening occurs with age and disease but may be prolonged in moderate-to-severe OSA. NEW & NOTEWORTHY Here, we show that moderate-to-severe obstructive sleep apnea is associated with longer telomeres, independent of age and cardiovascular risk factors, challenging the hypothesis that telomere shortening is a unidirectional process related to age/disease. A better understanding of the mechanisms underlying telomere dynamics may identify tar...
Source: AJP: Heart and Circulatory Physiology - November 6, 2017 Category: Cardiology Authors: Polonis, K., Somers, V. K., Becari, C., Covassin, N., Schulte, P. J., Druliner, B. R., Johnson, R. A., Narkiewicz, K., Boardman, L. A., Singh, P. Tags: RESEARCH ARTICLE Source Type: research

An update on hormone therapy in postmenopausal women: mini-review for the basic scientist
The worlds of observational, clinical, and basic science collided in 2002 with the publication of results of the Women’s Health Initiative (WHI), a large-scale, prospective, blinded, randomized-controlled trial designed to provide evidence regarding use of hormone treatment to prevent cardiovascular disease in menopausal women. The results of the WHI dramatically changed clinical practice, negatively impacted funding for hormone research, and left scientists to unravel the "why" of the results. Now over a decade and a half since the initial publication of the WHI results, basic and clinical scientists often...
Source: AJP: Heart and Circulatory Physiology - November 6, 2017 Category: Cardiology Authors: Miller, V. M., Harman, S. M. Tags: REVIEW Source Type: research

Role of pattern recognition receptors of the neurovascular unit in inflamm-aging
Aging is associated with chronic inflammation partly mediated by increased levels of damage-associated molecular patterns, which activate pattern recognition receptors (PRRs) of the innate immune system. Furthermore, many aging-related disorders are associated with inflammation. PRRs, such as Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain-like receptors (NLRs), are expressed not only in cells of the innate immune system but also in other cells, including cells of the neurovascular unit and cerebral vasculature forming the blood-brain barrier. In this review, we summarize our present knowledge abou...
Source: AJP: Heart and Circulatory Physiology - November 6, 2017 Category: Cardiology Authors: Wilhelm, I., Nyul-Toth, A., Kozma, M., Farkas, A. E., Krizbai, I. A. Tags: REVIEW Source Type: research

Preconditioning with the BKCa channel activator NS-1619 prevents ischemia-reperfusion-induced inflammation and mucosal barrier dysfunction: roles for ROS and heme oxygenase-1
Activation of large-conductance Ca2+-activated K+ (BKCa) channels evokes cell survival programs that mitigate intestinal ischemia and reperfusion (I/R) inflammation and injury 24 h later. The goal of the present study was to determine the roles of reactive oxygen species (ROS) and heme oxygenase (HO)-1 in delayed acquisition of tolerance to I/R induced by pretreatment with the BKCa channel opener NS-1619. Superior mesentery arteries were occluded for 45 min followed by reperfusion for 70 min in wild-type (WT) or HO-1-null (HO-1–/–) mice that were pretreated with NS-1619 or saline vehicle 24 h earlier. Intravita...
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: Dai, H., Wang, M., Patel, P. N., Kalogeris, T., Liu, Y., Durante, W., Korthuis, R. J. Tags: RESEARCH ARTICLE Source Type: research

Primed polymorphonuclear leukocytes from hemodialysis patients enhance monocyte transendothelial migration
Increased counts and priming of peripheral polymorphonuclear leukocytes (PMNLs) are associated with future or ongoing atherosclerosis; however, the role of PMNLs in enhancing monocyte transendothelial migration is still unclear. Our aims were to examine endothelial and monocyte activation, transmigration, and posttransmigration activation induced ex vivo by in vivo primed PMNLs and the effect of antioxidants on the activation. A unique ex vivo coculture system of three cell types was developed in this study, enabling interactions among the following: primary human umbilical vein endothelial cells (HUVECs), monocytes (THP-1...
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: Kliger, E., Kristal, B., Shapiro, G., Chezar, J., Sela, S. Tags: RESEARCH ARTICLE Source Type: research

Visualization of three pathways for macromolecule transport across cultured endothelium and their modification by flow
Transport of macromolecules across vascular endothelium and its modification by fluid mechanical forces are important for normal tissue function and in the development of atherosclerosis. However, the routes by which macromolecules cross endothelium, the hemodynamic stresses that maintain endothelial physiology or trigger disease, and the dependence of transendothelial transport on hemodynamic stresses are controversial. We visualized pathways for macromolecule transport and determined the effect on these pathways of different types of flow. Endothelial monolayers were cultured under static conditions or on an orbital shak...
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: Ghim, M., Alpresa, P., Yang, S.-W., Braakman, S. T., Gray, S. G., Sherwin, S. J., van Reeuwijk, M., Weinberg, P. D. Tags: RESEARCH ARTICLE Source Type: research

Shock and lethality with anthrax edema toxin in rats are associated with reduced arterial responsiveness to phenylephrine and are reversed with adefovir
Although edema toxin (ETx) and lethal toxin (LTx) contribute to Bacillus anthracis shock and lethality, the mechanisms underlying their cardiovascular effects are unclear. We have previously shown that ETx but not LTx inhibited phenylephrine-stimulated contraction of aortic rings prepared from healthy rats and that adefovir, a selective inhibitor of ETx cAMP production, blocked this effect. Here, we examined arterial function in rats that received 24-h ETx or LTx infusions. Compared with control rats, ETx reduced mean arterial pressure (MAP) and survival over 48 h (P ≤ 0.0003) and increased plasma cAMP at 4, 24, and 48 h (P
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: Suffredini, D. A., Li, Y., Xu, W., Moayeri, M., Leppla, S., Fitz, Y., Cui, X., Eichacker, P. Q. Tags: RESEARCH ARTICLE Source Type: research

Inhibitory actions of the NRG-1/ErbB4 pathway in macrophages during tissue fibrosis in the heart, skin, and lung
In this study, we hypothesized that the antifibrotic effect of NRG-1 in the heart is at least partially mediated through inhibitory effects on macrophages. We also hypothesized that the antifibrotic effect of NRG-1 may be active in other organs, such as the skin and lung. First, in a mouse model of angiotensin II (ANG II)-induced myocardial hypertrophy and fibrosis, NRG-1 treatment (20 µg·kg–1·day–1 ip) significantly attenuated myocardial hypertrophy and fibrosis and improved passive ventricular stiffness (4 wk). Interestingly, 1 wk after exposure to ANG II, NRG-1 already attenuated myocardi...
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: Vermeulen, Z., Hervent, A.-S., Dugaucquier, L., Vandekerckhove, L., Rombouts, M., Beyens, M., Schrijvers, D. M., De Meyer, G. R. Y., Maudsley, S., De Keulenaer, G. W., Segers, V. F. M. Tags: RESEARCH ARTICLE Source Type: research

Mineralocorticoids: the secret of muscle reflex dysfunction in hypertension?
(Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: Wang, H.-J. Tags: EDITORIAL FOCUS Source Type: research

How does pressure overload cause cardiac hypertrophy and dysfunction? High-ouabain affinity cardiac Na+ pumps are crucial
Left ventricular hypertrophy is frequently observed in hypertensive patients and is believed to be due to the pressure overload and cardiomyocyte stretch. Three recent reports on mice with genetically engineered Na+ pumps, however, have demonstrated that cardiac ouabain-sensitive α2-Na+ pumps play a key role in the pathogenesis of transaortic constriction-induced hypertrophy. Hypertrophy was delayed/attenuated in mice with mutant, ouabain-resistant α2-Na+ pumps and in mice with cardiac-selective knockout or transgenic overexpression of α2-Na+ pumps. The latter, seemingly paradoxical, findings can be expla...
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: Blaustein, M. P. Tags: REVIEW Source Type: research

Dietary modulation of oxylipins in cardiovascular disease and aging
Oxylipins are a group of fatty acid metabolites generated via oxygenation of polyunsaturated fatty acids and are involved in processes such as inflammation, immunity, pain, vascular tone, and coagulation. As a result, oxylipins have been implicated in many conditions characterized by these processes, including cardiovascular disease and aging. The best characterized oxylipins in relation to cardiovascular disease are derived from the -6 fatty acid arachidonic acid. These oxylipins generally increase inflammation, hypertension, and platelet aggregation, although not universally. Similarly, oxylipins derived from the -6 fatt...
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: Caligiuri, S. P. B., Parikh, M., Stamenkovic, A., Pierce, G. N., Aukema, H. M. Tags: REVIEW Source Type: research

Vascular niche contribution to age-associated neural stem cell dysfunction
Neural stem cells (NSCs) persist throughout life in the dentate gyrus and the ventricular-subventricular zone, where they continuously provide new neurons and some glia. These cells are found in specialized niches that regulate quiescence, activation, differentiation, and cell fate choice. A key aspect of the regulatory niche is the vascular plexus, which modulates NSC behavior during tissue homeostasis and regeneration. During aging, NSCs become depleted and dysfunctional, resulting in reduced neurogenesis and poor brain repair. In this review, we discuss the emerging evidence that changes in the vascular niche both struc...
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: Apple, D. M., Kokovay, E. Tags: REVIEW Source Type: research

Endothelial cell senescence with aging in healthy humans: prevention by habitual exercise and relation to vascular endothelial function
Cellular senescence is emerging as a key mechanism of age-related vascular endothelial dysfunction, but evidence in healthy humans is lacking. Moreover, the influence of lifestyle factors such as habitual exercise on endothelial cell (EC) senescence is unknown. We tested the hypothesis that EC senescence increases with sedentary, but not physically active, aging and is associated with vascular endothelial dysfunction. Protein expression (quantitative immunofluorescence) of p53, a transcription factor related to increased cellular senescence, and the cyclin-dependent kinase inhibitors p21 and p16 were 116%, 119%, and 128% g...
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: Rossman, M. J., Kaplon, R. E., Hill, S. D., McNamara, M. N., Santos-Parker, J. R., Pierce, G. L., Seals, D. R., Donato, A. J. Tags: RAPID REPORT Source Type: research

Temperature-dependent modulation of regional lymphatic contraction frequency and flow
This study demonstrates to what extent lymphatic vessel intrinsic contractility and lymph flow are modulated by temperature and that this modulation is dependent on the body district that the vessels belong to, suggesting a possible functional misbehavior should lymphatic vessels be exposed to a chronically different temperature. (Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: Solari, E., Marcozzi, C., Negrini, D., Moriondo, A. Tags: RESEARCH ARTICLE Source Type: research

Impact of electrical defibrillation on infarct size and no-reflow in pigs subjected to myocardial ischemia-reperfusion without and with ischemic conditioning
Ventricular fibrillation (VF) occurs frequently during myocardial ischemia-reperfusion (I/R) and must then be terminated by electrical defibrillation. We have investigated the impact of VF/defibrillation on infarct size (IS) or area of no reflow (NR) without and with ischemic conditioning interventions. Anesthetized pigs were subjected to 60/180 min of coronary occlusion/reperfusion. VF, as identified from the ECG, was terminated by intrathoracic defibrillation. The area at risk (AAR), IS, and NR were determined by staining techniques (patent blue, triphenyltetrazolium chloride, and thioflavin-S). Four experimental protoco...
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: Skyschally, A., Amanakis, G., Neuhäuser, M., Kleinbongard, P., Heusch, G. Tags: RESEARCH ARTICLE Source Type: research

A comparison of passive hindlimb cycling and active upper-limb exercise provides new insights into systolic dysfunction after spinal cord injury
Active upper-limb and passive lower-limb exercise are two interventions used in the spinal cord injury (SCI) population. Although the global cardiac responses have been previously studied, it is unclear how either exercise influences contractile cardiac function. Here, the cardiac contractile and volumetric responses to upper-limb (swim) and passive lower-limb exercise were investigated in rodents with a severe high-thoracic SCI. Animals were divided into control (CON), SCI no exercise (NO-EX), SCI passive hindlimb cycling (PHLC), or SCI swim (SWIM) groups. Severe contusion SCI was administered at the T2 level. PHLC and SW...
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: DeVeau, K. M., Harman, K. A., Squair, J. W., Krassioukov, A. V., Magnuson, D. S. K., West, C. R. Tags: RESEARCH ARTICLE Source Type: research

Muscle contraction induced arterial shear stress increases endothelial nitric oxide synthase phosphorylation in humans
We determined if local increases in brachial artery shear during repetitive muscle contractions induce changes in protein expression of endothelial nitric oxide synthase (eNOS) and/or phosphorylated (p-)eNOS at Ser1177, the primary activation site on eNOS, in endothelial cells (ECs) of humans. Seven young male subjects (25 ± 1 yr) performed 20 separate bouts (3 min each) of rhythmic forearm exercise at 20% of maximum over a 2-h period. Each bout of exercise was separated by 3 min of rest. An additional six male subjects (24 ± 1 yr) served as time controls (no exercise). ECs were freshly isolated from the brac...
Source: AJP: Heart and Circulatory Physiology - October 11, 2017 Category: Cardiology Authors: Casey, D. P., Ueda, K., Wegman-Points, L., Pierce, G. L. Tags: RAPID REPORT Source Type: research

Modulation of mesenteric collecting lymphatic contractions by {sigma}1-receptor activation and nitric oxide production
Recently, it has been reported that a -receptor antagonist could reduce inflammation-induced edema. Lymphatic vessels play an essential role in removing excess interstitial fluid. We tested the hypothesis that activation of -receptors would reduce or weaken collecting lymphatic contractions. We used isolated, cannulated rat mesenteric collecting lymphatic vessels to study contractions in response to the -receptor agonist afobazole in the absence and presence of different -receptor antagonists. We used RT-PCR and Western blot analysis to investigate whether these vessels express the 1-receptor and immunofluorescence confoca...
Source: AJP: Heart and Circulatory Physiology - October 11, 2017 Category: Cardiology Authors: Trujillo, A. N., Katnik, C., Cuevas, J., Cha, B. J., Taylor-Clark, T. E., Breslin, J. W. Tags: RESEARCH ARTICLE Source Type: research

Enhanced NO-dependent pulmonary vasodilation limits increased vasoconstrictor sensitivity in neonatal chronic hypoxia
Augmented vasoconstrictor reactivity is thought to play an important role in the development of chronic hypoxia (CH)-induced neonatal pulmonary hypertension. However, whether this response to CH results from pulmonary endothelial dysfunction and reduced nitric oxide (NO)-mediated vasodilation is not well understood. We hypothesized that neonatal CH enhances basal tone and pulmonary vasoconstrictor sensitivity by limiting NO-dependent pulmonary vasodilation. To test this hypothesis, we assessed the effects of the NO synthase (NOS) inhibitor N-nitro-l-arginine (l-NNA) on baseline pulmonary vascular resistance (PVR) and vasoc...
Source: AJP: Heart and Circulatory Physiology - October 11, 2017 Category: Cardiology Authors: Sheak, J. R., Weise-Cross, L., deKay, R. J., Walker, B. R., Jernigan, N. L., Resta, T. C. Tags: RESEARCH ARTICLE Source Type: research

Gq-activated fibroblasts induce cardiomyocyte action potential prolongation and automaticity in a three-dimensional microtissue environment
In conclusion, our data demonstrate that CF activation alone is capable of altering action potential and Ca2+ transient characteristics of CMs, leading to proarrhythmic electrical activity. Our results also emphasize the importance of a 3-D environment where cell-cell interactions are prevalent, underscoring that CF activation in 3-D tissue plays a significant role in modulating CM electrophysiology and arrhythmias. NEW & NOTEWORTHY In a three-dimensional microtissue model, which lowers baseline activation of cardiac fibroblasts but enables cell-cell, paracrine, and cell-extracellular matrix interactions, we demonstrat...
Source: AJP: Heart and Circulatory Physiology - October 11, 2017 Category: Cardiology Authors: Kofron, C. M., Kim, T. Y., King, M. E., Xie, A., Feng, F., Park, E., Qu, Z., Choi, B.- R., Mende, U. Tags: RESEARCH ARTICLE Source Type: research

Vitamin C mitigates oxidative/nitrosative stress and inflammation in doxorubicin-induced cardiomyopathy
Increase in oxidative/nitrosative stress is one of the mechanisms associated with the development of cardiotoxicity due to doxorubicin (Dox), a potent chemotherapy drug. Previously, we reported mitigation of Dox-induced oxidative/nitrosative stress and apoptosis by vitamin C (Vit C) in isolated cardiomyocytes. In the present in vivo study in rats, we investigated the effect of prophylactic treatment with Vit C on Dox-induced apoptosis, inflammation, oxidative/nitrosative stress, cardiac dysfunction, and Vit C transporter proteins. Dox (cumulative dose: 15 mg/kg) in rats reduced systolic and diastolic cardiac function and c...
Source: AJP: Heart and Circulatory Physiology - October 11, 2017 Category: Cardiology Authors: Akolkar, G., da Silva Dias, D., Ayyappan, P., Bagchi, A. K., Jassal, D. S., Salemi, V. M. C., Irigoyen, M. C., De Angelis, K., Singal, P. K. Tags: RESEARCH ARTICLE Source Type: research

Mineralocorticoid receptor antagonists attenuate exaggerated exercise pressor reflex responses in hypertensive rats
Exaggerated heart rate (HR) and blood pressure responses to exercise in hypertension are mediated, in part, by overactivity of the exercise pressor reflex (EPR). The mechanisms underlying this EPR dysfunction have not been fully elucidated. Previous studies have shown that stimulation of mineralocorticoid receptors (MRs) with exogenous administration of aldosterone in normal, healthy rats reproduces the EPR overactivity characteristic of hypertensive animals. Conversely, the purpose of this study was to examine whether antagonizing MR with spironolactone (SPIR) or eplerenone (EPL) in decerebrated hypertensive rats ameliora...
Source: AJP: Heart and Circulatory Physiology - October 11, 2017 Category: Cardiology Authors: Downey, R. M., Mizuno, M., Mitchell, J. H., Vongpatanasin, W., Smith, S. A. Tags: RESEARCH ARTICLE Source Type: research

Muscle sympathetic nerve activity and volume-regulating factors in healthy pregnant and nonpregnant women
Healthy, normotensive human pregnancies are associated with striking increases in both plasma volume and vascular sympathetic nerve activity (SNA). In nonpregnant humans, volume-regulatory factors including plasma osmolality, vasopressin, and the renin-angiotensin-aldosterone system have important modulatory effects on control of sympathetic outflow. We hypothesized that pregnancy would be associated with changes in the relationships between SNA (measured as muscle SNA) and volume-regulating factors, including plasma osmolality, plasma renin activity, and arginine vasopressin (AVP). We studied 46 healthy, normotensive youn...
Source: AJP: Heart and Circulatory Physiology - October 11, 2017 Category: Cardiology Authors: Charkoudian, N., Usselman, C. W., Skow, R. J., Staab, J. S., Julian, C. G., Stickland, M. K., Chari, R. S., Khurana, R., Davidge, S. T., Davenport, M. H., Steinback, C. D. Tags: RESEARCH ARTICLE Source Type: research

Circulating acylcarnitine profile in human heart failure: a surrogate of fatty acid metabolic dysregulation in mitochondria and beyond
This study aimed at testing the hypothesis that HF patients with reduced ejection fraction display systemic perturbations in levels of energy-related metabolites, especially those reflecting dysregulation of FA metabolism, namely, acylcarnitines (ACs). Circulating metabolites were assessed using mass spectrometry (MS)-based methods in two cohorts. The main cohort consisted of 72 control subjects and 68 HF patients exhibiting depressed left ventricular ejection fraction (25.9 ± 6.9%) and mostly of ischemic etiology with ≥2 comorbidities. HF patients displayed marginal changes in plasma levels of tricarboxylic acid...
Source: AJP: Heart and Circulatory Physiology - October 11, 2017 Category: Cardiology Authors: Ruiz, M., Labarthe, F., Fortier, A., Bouchard, B., Thompson Legault, J., Bolduc, V., Rigal, O., Chen, J., Ducharme, A., Crawford, P. A., Tardif, J.-C., Des Rosiers, C. Tags: RESEARCH ARTICLE Source Type: research

Mitochondrial function in engineered cardiac tissues is regulated by extracellular matrix elasticity and tissue alignment
Mitochondria in cardiac myocytes are critical for generating ATP to meet the high metabolic demands associated with sarcomere shortening. Distinct remodeling of mitochondrial structure and function occur in cardiac myocytes in both developmental and pathological settings. However, the factors that underlie these changes are poorly understood. Because remodeling of tissue architecture and extracellular matrix (ECM) elasticity are also hallmarks of ventricular development and disease, we hypothesize that these environmental factors regulate mitochondrial function in cardiac myocytes. To test this, we developed a new procedur...
Source: AJP: Heart and Circulatory Physiology - October 11, 2017 Category: Cardiology Authors: Lyra-Leite, D. M., Andres, A. M., Petersen, A. P., Ariyasinghe, N. R., Cho, N., Lee, J. A., Gottlieb, R. A., McCain, M. L. Tags: RESEARCH ARTICLE Source Type: research

TNF-{alpha} receptor 1 knockdown in the subfornical organ ameliorates sympathetic excitation and cardiac hemodynamics in heart failure rats
In systolic heart failure (HF), circulating proinflammatory cytokines upregulate inflammation and renin-angiotensin system (RAS) activity in cardiovascular regions of the brain, contributing to sympathetic excitation and cardiac dysfunction. Important among these is the subfornical organ (SFO), a forebrain circumventricular organ that lacks an effective blood-brain barrier and senses circulating humors. We hypothesized that the tumor necrosis factor-α (TNF-α) receptor 1 (TNFR1) in the SFO contributes to sympathetic excitation and cardiac dysfunction in HF rats. Rats received SFO microinjections of a TNFR1 shRNA...
Source: AJP: Heart and Circulatory Physiology - October 11, 2017 Category: Cardiology Authors: Yu, Y., Wei, S.-G., Weiss, R. M., Felder, R. B. Tags: RESEARCH ARTICLE Source Type: research

Analysis of decreases in systemic arterial pressure and heart rate in response to the hydrogen sulfide donor sodium sulfide
The objective of the present study was to investigate the effect of H2S on the electrocardiogram and examine the relationship between H2S-induced changes in heart rate (HR), mean arterial pressure (MAP), and respiratory function. Intravenous administration of the H2S donor Na2S in the anesthetized Sprague-Dawley rat decreased MAP and HR and produced changes in respiratory function. The administration of Na2S significantly increased the RR interval at some doses but had no effect on PR or corrected QT(n)-B intervals. In experiments where respiration was maintained with a mechanical ventilator, we observed that Na2S-induced ...
Source: AJP: Heart and Circulatory Physiology - October 11, 2017 Category: Cardiology Authors: Swan, K. W., Song, B. M., Chen, A. L., Chen, T. J., Chan, R. A., Guidry, B. T., Katakam, P. V. G., Kerut, E. K., Giles, T. D., Kadowitz, P. J. Tags: RESEARCH ARTICLE Source Type: research

Circumventing a broken heart: cytokines and the subfornical organ
(Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - October 11, 2017 Category: Cardiology Authors: Yao, S. T., McKinley, M. J., May, C. N. Tags: EDITORIAL FOCUS Source Type: research

Prolonged sitting leg vasculopathy: contributing factors and clinical implications
Atherosclerotic peripheral artery disease primarily manifests in the medium- to large-sized conduit arteries of the lower extremities. However, the factors underlying this increased vulnerability of leg macrovasculature to disease are largely unidentified. On the basis of recent studies, we propose that excessive time spent in the sitting position and the ensuing reduction in leg blood flow-induced shear stress cause endothelial cell dysfunction, a key predisposing factor to peripheral artery disease. In particular, this review summarizes the findings from laboratory-based sitting studies revealing acute leg vascular dysfu...
Source: AJP: Heart and Circulatory Physiology - October 11, 2017 Category: Cardiology Authors: Padilla, J., Fadel, P. J. Tags: REVIEW Source Type: research

Pathophysiology of cardiorenal syndrome in patients with heart failure: potential therapeutic targets
Despite the development of pharmacological inventions and new nonpharmacological techniques to prevent and treat heart failure (HF), the mortality rate in patients with symptomatic HF remains high. To conquer these difficulties, the pathophysiology of HF should be considered within a wide range of views. Given the diverse mechanisms of HF pathophysiology, renal and cardiac functions have close and complementary interconnections. Recent studies have suggested that communication between the kidney and heart through bidirectional pathways causes significant pathological changes. This review summarizes the pathophysiology of c...
Source: AJP: Heart and Circulatory Physiology - October 11, 2017 Category: Cardiology Authors: Takahama, H., Kitakaze, M. Tags: REVIEW Source Type: research

Temporal changes in the exercise pressor reflex in type 1 diabetic rats
We examined, in decerebrate male and female T1DM [streptozotocin (STZ)] and healthy control (CTL) rats, pressor and cardioaccelerator responses to isometric contraction of the hindlimb muscles during the early and late stages of the disease. STZ (50 mg/kg) was injected to induce diabetes, and experiments were conducted at 1, 3, and 6 wk after injection. On the day of the experiment, we statically contracted the hindlimb muscles by stimulating the sciatic nerve and measured changes in mean arterial pressure and heart rate. We found that the pressor but not cardioaccelerator response was exaggerated in STZ rats at 1 wk (STZ:...
Source: AJP: Heart and Circulatory Physiology - October 1, 2017 Category: Cardiology Authors: Grotle, A.-K., Garcia, E. A., Huo, Y., Stone, A. J. Tags: RAPID REPORT Source Type: research

Anomalous baroreflex functionality inherent in floxed and Cre-Lox mice: an overlooked physiological phenotype
The last two decades have seen the emergence of Cre-Lox recombination as one of the most powerful and versatile technologies for cell-specific genetic engineering of mammalian cells. Understandably, the primary concerns in the practice of Cre-Lox recombination are whether the predicted genome has been correctly modified and the targeted phenotypes expressed. Rarely are the physiological conditions of the animals routinely examined because the general assumption is that they are normal. Based on corroborative results from radiotelemetric recording, power spectral analysis, and magnetic resonance imaging/diffusion tensor ima...
Source: AJP: Heart and Circulatory Physiology - October 1, 2017 Category: Cardiology Authors: Tsai, C.-Y., Poon, Y.-Y., Chen, C.-H., Chan, S. H. H. Tags: RAPID REPORT Source Type: research

Intracoronary delivery of recombinant TIMP-3 after myocardial infarction: effects on myocardial remodeling and function
Ischemia-reperfusion (IR) and myocardial infarction (MI) cause adverse left ventricular (LV) remodeling and heart failure and are facilitated by an imbalance in matrix metalloproteinase (MMP) activation and the endogenous tissue inhibitors of metalloproteinase (TIMPs). We have identified that myocardial injections of recombinant TIMP-3 (rTIMP-3; human full length) can interrupt post-MI remodeling. However, whether and to what degree intracoronary delivery of rTIMP-3 post-IR is feasible and effective remained to be established. Pigs (25 kg) underwent coronary catheterization and balloon occlusion of the left anterior descen...
Source: AJP: Heart and Circulatory Physiology - October 1, 2017 Category: Cardiology Authors: Barlow, S. C., Doviak, H., Jacobs, J., Freeburg, L. A., Perreault, P. E., Zellars, K. N., Moreau, K., Villacreses, C. F., Smith, S., Khakoo, A. Y., Lee, T., Spinale, F. G. Tags: RESEARCH ARTICLE Source Type: research

Uncovering novel roles for matrix metalloproteinases in preeclampsia
(Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - October 1, 2017 Category: Cardiology Authors: Foote, C. A., Martinez-Lemus, L. A. Tags: EDITORIAL FOCUS Source Type: research

5-HT causes splanchnic venodilation
Serotonin [5-hydroxytryptamine (5-HT)] causes relaxation of the isolated superior mesenteric vein, a splanchnic blood vessel, through activation of the 5-HT7 receptor. As part of studies designed to identify the mechanism(s) through which chronic (≥24 h) infusion of 5-HT lowers blood pressure, we tested the hypothesis that 5-HT causes in vitro and in vivo splanchnic venodilation that is 5-HT7 receptor dependent. In tissue baths for measurement of isometric contraction, the portal vein and abdominal inferior vena cava relaxed to 5-HT and the 5-HT1/7 receptor agonist 5-carboxamidotryptamine; relaxation was abolished by th...
Source: AJP: Heart and Circulatory Physiology - September 12, 2017 Category: Cardiology Authors: Seitz, B. M., Orer, H. S., Krieger-Burke, T., Darios, E. S., Thompson, J. M., Fink, G. D., Watts, S. W. Tags: RESEARCH ARTICLE Source Type: research

Regional heterogeneity in the mechanisms of myogenic tone in hamster arterioles
Myogenic tone is an important feature of arterioles and resistance arteries, but the mechanisms responsible for this hallmark characteristic remain unclear. We used pharmacological inhibitors to compare the roles played by phospholipase C (PLC; 10 μM U73122), inositol 1,4,5-trisphosphate receptors (IP3Rs; 100 μM 2-aminoethoxydiphenylborane), protein kinase C (10 μM bisindolylmaleimide I), angiotensin II type 1 receptors (1 μM losartan), Rho kinase (10 nM–30 μM Y27632 or 300 nM H1152), stretch-activated ion channels (10 nM–1 μM Gd3+ or 5 μM spider venom toxin GsMTx-4) and L-type voltage-gate...
Source: AJP: Heart and Circulatory Physiology - September 12, 2017 Category: Cardiology Authors: Jackson, W. F., Boerman, E. M. Tags: RESEARCH ARTICLE Source Type: research

Folic acid ingestion improves skeletal muscle blood flow during graded handgrip and plantar flexion exercise in aged humans
Skeletal muscle blood flow is attenuated in aged humans performing dynamic exercise, which is due, in part, to impaired local vasodilatory mechanisms. Recent evidence suggests that folic acid improves cutaneous vasodilation during localized and whole body heating through nitric oxide-dependent mechanisms. However, it is unclear whether folic acid improves vasodilation in other vascular beds during conditions of increased metabolism (i.e., exercise). The purpose of this study was to test the hypothesis that folic acid ingestion improves skeletal muscle blood flow in aged adults performing graded handgrip and plantar flexion...
Source: AJP: Heart and Circulatory Physiology - September 12, 2017 Category: Cardiology Authors: Romero, S. A., Gagnon, D., Adams, A. N., Moralez, G., Kouda, K., Jaffery, M. F., Cramer, M. N., Crandall, C. G. Tags: RESEARCH ARTICLE Source Type: research

The carotid baroreflex modifies the pressor threshold of the muscle metaboreflex in humans
The purpose of the present study was to test our hypothesis that unloading the carotid baroreceptors alters the threshold and gain of the muscle metaboreflex in humans. Ten healthy subjects performed a static handgrip exercise at 50% of maximum voluntary contraction. Contraction was sustained for 15, 30, 45, and 60 s and was followed by 3 min of forearm circulatory arrest, during which forearm muscular pH is known to decrease linearly with increasing contraction time. The carotid baroreceptors were unloaded by applying 0.1-Hz sinusoidal neck pressure (oscillating from +15 to +50 mmHg) during ischemia. We estimated the thre...
Source: AJP: Heart and Circulatory Physiology - September 12, 2017 Category: Cardiology Authors: Ichinose, M., Ichinose-Kuwahara, T., Watanabe, K., Kondo, N., Nishiyasu, T. Tags: RESEARCH ARTICLE Source Type: research

MicroRNA-124 controls human vascular smooth muscle cell phenotypic switch via Sp1
Phenotypic switch of vascular smooth muscle cells (VSMCs) plays an important role in the pathogenesis of atherosclerosis and aortic dissection. However, the mechanisms of phenotypic modulation are still unclear. MicroRNAs have emerged as important regulators of VSMC function. We recently found that microRNA-124 (miR-124) was downregulated in proliferative vascular diseases that were characterized by a VSMC phenotypic switch. Therefore, we speculated that the aberrant expression of miR-124 might play a critical role in human aortic VSMC phenotypic switch. Using quantitative RT-PCR, we found that miR-124 was dramatically dow...
Source: AJP: Heart and Circulatory Physiology - September 12, 2017 Category: Cardiology Authors: Tang, Y., Yu, S., Liu, Y., Zhang, J., Han, L., Xu, Z. Tags: RESEARCH ARTICLE Source Type: research

Cardiac fibroblast transcriptome analyses support a role for interferogenic, profibrotic, and inflammatory genes in anti-SSA/Ro-associated congenital heart block
This study provides in vivo and in vitro transcriptome-support that injury may be mediated by an effect of Type I Interferon on fetal fibroblasts. (Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - September 12, 2017 Category: Cardiology Authors: Clancy, R. M., Markham, A. J., Jackson, T., Rasmussen, S. E., Blumenberg, M., Buyon, J. P. Tags: RESEARCH ARTICLE Source Type: research

Remodeling of repolarization and arrhythmia susceptibility in a myosin-binding protein C knockout mouse model
In conclusion, decrease in repolarizing K+ currents in MyBPC KO ventricular myocytes contributes to AP and corrected QT interval prolongation and could account for the arrhythmia susceptibility. NEW & NOTEWORTHY Ventricular myocytes isolated from the myosin-binding protein C knockout hypertrophic cardiomyopathy mouse model demonstrate decreased repolarizing K+ currents and action potential and QT interval prolongation, linking cellular repolarization abnormalities with arrhythmia susceptibility and the risk for sudden cardiac death in hypertrophic cardiomyopathy. (Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - September 12, 2017 Category: Cardiology Authors: Toib, A., Zhang, C., Borghetti, G., Zhang, X., Wallner, M., Yang, Y., Troupes, C. D., Kubo, H., Sharp, T. E., Feldsott, E., Berretta, R. M., Zalavadia, N., Trappanese, D. M., Harper, S., Gross, P., Chen, X., Mohsin, S., Houser, S. R. Tags: RESEARCH ARTICLE Source Type: research

Revisiting protein acetylation and myocardial fatty acid oxidation
(Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - September 12, 2017 Category: Cardiology Authors: Al Batran, R., Ussher, J. R. Tags: EDITORIAL FOCUS Source Type: research

Metabolic remodeling in hypertrophied and failing myocardium: a review
The energy starvation hypothesis proposes that maladaptive metabolic remodeling antedates, initiates, and maintains adverse contractile dysfunction in heart failure (HF). Better understanding of the cardiac metabolic phenotype and metabolic signaling could help identify the role metabolic remodeling plays within HF and the conditions known to transition toward HF, including "pathological" hypertrophy. In this review, we discuss metabolic phenotype and metabolic signaling in the contexts of pathological hypertrophy and HF. We discuss the significance of alterations in energy supply (substrate utilization, oxidativ...
Source: AJP: Heart and Circulatory Physiology - September 12, 2017 Category: Cardiology Authors: Peterzan, M. A., Lygate, C. A., Neubauer, S., Rider, O. J. Tags: REVIEW Source Type: research

Metabolic reprogramming via PPAR{alpha} signaling in cardiac hypertrophy and failure: From metabolomics to epigenetics
Studies using omics-based approaches have advanced our knowledge of metabolic remodeling in cardiac hypertrophy and failure. Metabolomic analysis of the failing heart has revealed global changes in mitochondrial substrate metabolism. Peroxisome proliferator-activated receptor-α (PPARα) plays a critical role in synergistic regulation of cardiac metabolism through transcriptional control. Metabolic reprogramming via PPARα signaling in heart failure ultimately propagates into myocardial energetics. However, emerging evidence suggests that the expression level of PPARα per se does not always explain the...
Source: AJP: Heart and Circulatory Physiology - September 12, 2017 Category: Cardiology Authors: Warren, J. S., Oka, S.-i., Zablocki, D., Sadoshima, J. Tags: REVIEW Source Type: research

The human coronary vasodilatory response to acute mental stress is mediated by neuronal nitric oxide synthase
Mental stress-induced ischemia approximately doubles the risk of cardiac events in patients with coronary artery disease, yet the mechanisms underlying changes in coronary blood flow in response to mental stress are poorly characterized. Neuronal nitric oxide synthase (nNOS) regulates basal coronary blood flow in healthy humans and mediates mental stress-induced vasodilation in the forearm. However, its possible role in mental stress-induced increases in coronary blood flow is unknown. We studied 11 patients (6 men and 5 women, mean age: 58 ± 14 yr) undergoing elective diagnostic cardiac catheterization and assessed...
Source: AJP: Heart and Circulatory Physiology - September 5, 2017 Category: Cardiology Authors: Khan, S. G., Melikian, N., Shabeeh, H., Cabaco, A. R., Martin, K., Khan, F., OGallagher, K., Chowienczyk, P. J., Shah, A. M. Tags: RESEARCH ARTICLE Source Type: research

Significant role of the cardiopostural interaction in blood pressure regulation during standing
In this study, we aimed to assess the role of the cardiopostural interaction in relation to cardiac baroreflex in blood pressure regulation under orthostatic stress before and after mild exercise. Physiological variables representing cardiovascular control (heart rate and systolic blood pressure), lower limb muscle activation (electromyography), and postural sway (center of pressure derived from force and moment data during sway) were measured from 17 healthy participants (25 ± 2 yr, 9 men and 8 women) during a sit-to-stand test before and after submaximal exercise. The cardiopostural control (characterized by baror...
Source: AJP: Heart and Circulatory Physiology - September 5, 2017 Category: Cardiology Authors: Xu, D., Verma, A. K., Garg, A., Bruner, M., Fazel-Rezai, R., Blaber, A. P., Tavakolian, K. Tags: RESEARCH ARTICLE Source Type: research