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G Protein-Coupled Estrogen Receptor Protects From Angiotensin II-Induced Increases in Pulse Pressure and Oxidative Stress
Our previous work showed that the G protein-coupled estrogen receptor (GPER) is protective in the vasculature and kidneys during angiotensin (Ang) II-dependent hypertension by inhibiting oxidative stress. The goal of the current study was to assess the impact of GPER deletion on sex differences in Ang II-induced hypertension and oxidative stress. Male and female wildtype and GPER knockout mice were implanted with radiotelemetry probes for measurement of baseline blood pressure before infusion of Ang II (700 ng/kg/min) for two weeks. Mean arterial pressure was increased to the same extent in all groups, but female wildtype ...
Source: Frontiers in Endocrinology - August 26, 2019 Category: Endocrinology Source Type: research

AT1 Receptors in the Subfornical Organ Modulate Arterial Pressure and the Baroreflex In Two-kidney One-clip Hypertensive Rats.
Abstract The subfornical organ (SFO), a forebrain circumventricular organ that lies outside the blood brain barrier, has been implicated in arterial pressure and baroreflex responses to angiotensin II (Ang II). We tested whether pharmacologic inhibition or selective silencing of SFO AT1 receptors (AT1R) of two-kidney one-clip rats with elevated plasma Ang II decreases resting arterial pressure and renal sympathetic nerve activity (RSNA) and/or modulates arterial baroreflex responses of heart rate and RSNA. Male Sprague Dawley rats underwent renal artery clipping (2K-1C) or sham-clipping (Sham). Six weeks later, co...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - January 9, 2019 Category: Physiology Authors: Rossi NF, Zenner Z, Rishi AK, Levi E, Maliszewska-Scislo M Tags: Am J Physiol Regul Integr Comp Physiol Source Type: research

Losartan protects against cerebral ischemia/reperfusion-induced apoptosis through β-arrestin1-mediated phosphorylation of Akt.
In this study, we investigated whether losartan protected against cerebral I/R injury by reducing apoptosis and the possible signaling pathways. Wistar rats were pretreated for 14 days with 5mg/kg losartan, and then subjected to middle cerebral artery occlusion (MCAO) for 2h followed by reperfusion. Meanwhile, PC12 cells pretreated with losartan were exposed to oxygen-glucose deprivation-reoxygenation (OGD/R), an in vitro model of cerebral ischemia. Our results showed that administration of losartan significantly inhibited the apoptosis by decreasing the number of apoptotic cells, decreasing the protein level of cleaved ca...
Source: European Journal of Pharmacology - August 24, 2017 Category: Drugs & Pharmacology Authors: Chen L, Ren Z, Wei X, Wang S, Wang Y, Cheng Y, Gao H, Liu H Tags: Eur J Pharmacol Source Type: research

Renin-angiotensin system activation accelerates atherosclerosis in experimental renal failure by promoting endoplasmic reticulum stress-related inflammation.
In this study, we investigated the association between the renin-angiotensin system (RAS), endoplasmic reticulum (ER) stress and atherosclerosis (AS) in uremic apolipoprotein E knockout (apoE-/-) mice. Mild uremia was induced by a 5/6 nephrectomy (5/6 Nx) in 10-week-old apoE-/- mice. Four weeks after nephrectomy, the mice received losartan or no treatment for 16 weeks. Sham-operated mice served as the controls. We found that uremia accelerated AS at the aortic root. The activation of ER stress and the significant upregulation of pro-inflammatory cytokines and chemokines were observed in the uremic mice. Phosphoryla...
Source: International Journal of Molecular Medicine - January 11, 2017 Category: Molecular Biology Authors: Yang J, Zhang X, Yu X, Tang W, Gan H Tags: Int J Mol Med Source Type: research

LIPUS suppressed LPS ‐induced IL‐1α through the inhibition of NF‐κB nuclear translocation via AT1‐PLCβ pathway in MC3T3‐E1
This article is protected by copyright. All rights reserved
Source: Journal of Cellular Physiology - January 6, 2017 Category: Cytology Authors: Mayu Nagao, Natsuko Tanabe, Soichiro Manaka, Masako Naito, Kumiko Nakai, Tadahiro Takayama, Takayuki Kawato, Go Torigoe, Jumpei Sekino, Naoya Tsukune, Masao Maeno, Naoto Suzuki, Shuichi Sato Tags: ORIGINAL RESEARCH ARTICLE Source Type: research

H2S inhibits angiotensin II-induced atrial Kv1.5 upregulation by attenuating Nox4-mediated ROS generation during atrial fibrillation.
In conclusion, our study indicates that H2S downregulates Ang II-induced atrial Kv1.5 expression by attenuating Nox4-related ROS-triggered P-Smad2/3 and P-ERK 1/2 activation during AF. H2S supplementation would be beneficial for AF treatment via the suppression of atrial Kv1.5 expression. PMID: 28011270 [PubMed - as supplied by publisher]
Source: Biochemical and Biophysical Research communications - December 19, 2016 Category: Biochemistry Authors: Lu G, Xu C, Tang K, Zhang J, Li Q, Peng L, Wang Y, Huang Z, Gao X Tags: Biochem Biophys Res Commun Source Type: research

CD2-associated protein/phosphoinositide 3-kinase signaling has a preventive role in angiotensin II-induced podocyte apoptosis.
Abstract Angiotensin II (Ang II) works as a paracrine or autocrine cytokine agent to regulate renal functions and promotes podocytes dysfunction directly or indirectly, causing proteinuria. The glomerular slit diaphragm (SD) serves as a size-selective barrier and is linked to the actin-based cytoskeleton by adaptor proteins, including CD2-associated protein (CD2AP). Therefore, damages to CD2AP affect not only the function of the SD, but also directly disrupt the podocyte cytoskeleton, leading to proteinuria. In addition, CD2AP can facilitate the nephrin-induced phosphoinositide 3-kinase (PI3-K)/Akt signaling, whic...
Source: The International Journal of Biochemistry and Cell Biology - August 29, 2016 Category: Biochemistry Authors: Park HY, Seong SB, Min SY, Ha TS Tags: Int J Biochem Cell Biol Source Type: research

High Potassium Promotes Mutual Interaction between (Pro)Renin Receptor and the Local Renin-Angiotensin-Aldosterone System in Rat IMCD Cells.
Abstract (Pro)renin receptor (PRR) is predominantly expressed in the collecting duct (CD) with unclear functional implication. It is not known whether CD PRR is regulated by high potassium (HK). Here, we aimed to investigate the effect of HK on PRR expression and its role in regulation of aldosterone synthesis and release in the CD. In primary rat inner medullary CD cells, HK augmented PRR expression and soluble PPR (sPRR) release in a time- and dose- dependent manner, which was attenuated by PRR siRNA, eplerenone, and losartan. HK upregulated aldosterone release in parallel with an increase of CYP11B2 (cytochrome...
Source: Am J Physiol Cell Ph... - August 16, 2016 Category: Cytology Authors: Xu C, Fang H, Zhou L, Lu A, Yang T Tags: Am J Physiol Cell Physiol Source Type: research

Abstract 5109: The CARMA3-Bcl10-MALT1 signalosome mediates NF-{kappa}B activation and cellular invasion in AGTR1-positive breast cancer
Angiotensin II (Ang II) is a potent vasoconstrictor and vascular pro-inflammatory mediator, known classically for its role in promoting arterial dysfunction. Many of these pathogenic effects result from activation of NF-κB in response to stimulation of the type-1 Ang II receptor (AGTR1), a G protein-coupled receptor. We previously discovered that a complex composed of three proteins, CARMA3, Bcl10 and MALT1 (CBM signalosome) mediates AGTR1-dependent activation of NF-κB in vascular cells. Despite its principal role in vascular pathobiology, we recently found that AGTR1 is aberrantly overexpressed in 10-20% of breast cance...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Ekambaram, P., Hubel, N., Lee, J.-Y., Klei, L., Concel, V., Delekta, P., Tomlins, S., McAllister-Lucas, L., Lucas, P. Tags: Tumor Biology Source Type: research

Angiotensin II regulates brain (pro)renin receptor expression through activation of cAMP response element-binding protein
We reported that brain (pro)renin receptor (PRR) expression levels are elevated in DOCA-salt-induced hypertension; however, the underlying mechanism remained unknown. To address whether ANG II type 1 receptor (AT1R) signaling is involved in this regulation, we implanted a DOCA pellet and supplied 0.9% saline as the drinking solution to C57BL/6J mice. Sham pellet-implanted mice that were provided regular drinking water served as controls. Concurrently, mice were intracerebroventricularly infused with the AT1R blocker losartan, angiotensin-converting-enzyme inhibitor captopril, or artificial cerebrospinal fluid for 3 wk. Int...
Source: AJP: Regulatory, Integrative and Comparative Physiology - July 15, 2015 Category: Physiology Authors: Li, W., Liu, J., Hammond, S. L., Tjalkens, R. B., Saifudeen, Z., Feng, Y. Tags: Cardiovascular and Renal Integration Source Type: research

TRIF Promotes Angiotensin II-Induced Cross-talk between Fibroblasts and Macrophages in Atrial Fibrosis.
CONCLUSIONS: Our data demonstrated that TRIF may be a crucial factor promoting the interaction between atrial fibroblasts and macrophages, leading to atrial fibrosis. PMID: 26056004 [PubMed - as supplied by publisher]
Source: Biochemical and Biophysical Research communications - June 5, 2015 Category: Biochemistry Authors: Chen XQ, Zhang DL, Zhang MJ, Guo M, Zhan YY, Liu F, Jiang WF, Zhou L, Zhao L, Wang QX, Liu X Tags: Biochem Biophys Res Commun Source Type: research

Angiotensin II regulates brain (pro)renin receptor expression through activation of cAMP response element-binding protein.
We reported that brain (pro)renin receptor (PRR) expression levels are elevated in deoxycorticosterone acetate (DOCA)-salt-induced hypertension; however, the underlying mechanism remained unknown. To address whether angiotensin (Ang II) type 1 receptor (AT1R) signaling is involved in this regulation, we implanted a DOCA pellet and supplying 0.9% saline as the drinking solution to C57BL/6J mice; SHAM pellet-implanted mice provided regular drinking water served as controls. Concurrently, mice were intracerebroventricularly (ICV) infused with the AT1R blocker losartan, angiotensin converting-enzyme inhibitor captopril, or art...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - May 20, 2015 Category: Physiology Authors: Li W, Liu J, Hammond SL, Tjalkens RB, Saifudeen Z, Feng Y Tags: Am J Physiol Regul Integr Comp Physiol Source Type: research

Molecular regulation of the expression of leptin by hypoxia in human coronary artery smooth muscle cells
Conclusion: Hypoxia in HCASMCs increases leptin expression through the induction of AngII, ROS, and the JNK pathway to enhance atherosclerosis in HCASMCs.
Source: Journal of Biomedical Science - January 9, 2015 Category: Biomedical Science Authors: Chiung-Zuan ChiuBao-Wei WangKou-Gi Shyu Source Type: research

Mechanisms of AT1a receptor-mediated uptake of angiotensin II by proximal tubule cells: a novel role of the multiligand endocytic receptor megalin
The present study tested the hypothesis that the multiligand endocytic receptor megalin is partially involved in the uptake of ANG II and downstream signaling responses in mouse proximal tubule cells (mPCT) by interacting with AT1a receptors. mPCT cells of wild-type (WT) and AT1a receptor-deficient (AT1a-KO) mice were treated with vehicle, the AT1 receptor blocker losartan (10 μM), or a selective megalin small interfering (si) RNA for 48 h. The uptake of fluorescein (FITC)-labeled ANG II (10 nM, 37°C) and downstream signaling responses were analyzed by fluorescence imaging and Western blotting. AT1a receptors and me...
Source: AJP: Renal Physiology - July 15, 2014 Category: Urology & Nephrology Authors: Li, X. C., Zhuo, J. L. Tags: INNOVATIVE METHODOLOGY Source Type: research

Enhanced expression of Gqα and PLCβ1 proteins contribute to vascular smooth muscle cell Hypertrophy in SHR: role of endogenous angiotensin II and endothelin-1.
Abstract Vascular Gqα signaling has been shown to contribute to cardiac hypertrophy. In addition, angiotensin II (Ang II) was shown to induce VSMC hypertrophy through Gqα signaling, however, the studies on the role of Gqα and PLCβ1 proteins in VSMC hypertrophy in animal model are lacking. The present study was therefore undertaken to examine the role of Gqα/PLCβ1 proteins and the signaling pathways in VSMC hypertrophy using spontaneously hypertensive rats (SHR). VSMC from 16 week-old SHR and not from 12 week-old SHR exhibited enhanced levels of Gqα/PLCβ1 proteins as compared to age-matched Wistar-Kyoto (WK...
Source: American Journal of Physiology. Cell Physiology - April 23, 2014 Category: Cytology Authors: Atef ME, Anand-Srivastava MB Tags: Am J Physiol Cell Physiol Source Type: research

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