Enalapril/Carvedilol for Prevention of Chemotherapy-Induced Heart Failure An End to the Problem
I read with great interest the article by Bosch et al. (1) looking at enalapril and carvedilol for prevention of chemotherapy-induced left ventricular systolic dysfunction (LVSD). (Source: Journal of the American College of Cardiology: Cardiovascular Interventions)
Source: Journal of the American College of Cardiology: Cardiovascular Interventions - December 17, 2013 Category: Cardiology Source Type: research

Enalapril and Carvedilol for Preventing Chemotherapy-Induced Left Ventricular Systolic Dysfunction
We read with great interest the article by Bosch et al. (1). We congratulate the authors for their work, which sheds new light on the potential for preventing cardiotoxic effects of anticancer therapies. However, there are a few aspects that, in our opinion, need clarification. (Source: Journal of the American College of Cardiology: Cardiovascular Interventions)
Source: Journal of the American College of Cardiology: Cardiovascular Interventions - December 17, 2013 Category: Cardiology Source Type: research

Reply Enalapril and Carvedilol for Preventing Chemotherapy-Induced Left Ventricular Systolic Dysfunction in Patients With Malignant Hemopathies
We thank Dr. Golwala and Dr. Spallarossa and colleagues for their interest in our study. Both ask about the lack of association found in our study (1) between troponin elevation and benefit from pharmacological intervention. The value of troponins to predict left ventricular systolic dysfunction (LVSD) has been reported with anthracyclines but not with other drugs (2). However, we do not believe that our results are contradictory to those of Cardinale et al. (3); differences in the patient population, intensity and type of chemotherapy, and protocol design of both studies may account for their different resu...
Source: Journal of the American College of Cardiology: Cardiovascular Interventions - December 17, 2013 Category: Cardiology Source Type: research

A Randomized, Double-Blind Trial of Lisinopril and Losartan for the Treatment of Cardiomyopathy in Duchenne Muscular Dystrophy
In conclusion, there is no difference between the effects of lisinopril versus losartan on EF improvement in DMD boys with CM. The drugs were safe. Thus, this study opens the opportunity to study muscle function in younger boys with DMD to see if the skeletal muscle improvement seen in the mdx mouse following treatment with an ARB might also be demonstrated in DMD boys. 17 Competing Interests The authors have declared that no competing interests exist. Correspondence Hugh D. Allen MD, Heart Center, Texas Children’s Hospital, 6621 Fannin St. Suite 19469, Houston, TX, 77030 E-mail: hdallen@texaschildrens.org Auth...
Source: PLOS Currents Muscular Dystrophy - December 12, 2013 Category: Neurology Authors: Hugh D. Allen Source Type: research

The direct renin inhibitor aliskiren localizes and persists in rat kidneys
The aims of this study were to 1) determine whether renal localization of aliskiren and its antihypertensive and renoprotective effects persist after administration of the drug is stopped and 2) define the renal localization of aliskiren by light microscopy autoradiography. Hypertensive double transgenic rats (dTGR) overexpressing genes for human renin and angiotensinogen were treated with aliskiren (3 mg·kg–1·day–1 sc; osmotic minipumps) or enalapril (18 mg/l in drinking water). After a 2-wk treatment, dTGR were assigned to either continued treatment with aliskiren ("continued"), or to ...
Source: AJP: Renal Physiology - December 1, 2013 Category: Urology & Nephrology Authors: Feldman, D. L., Jin, L., Xuan, H., Persohn, E., Zhou, W., Schuetz, H., Park, J.-K., Muller, D. N., Luft, F. C. Tags: ARTICLES Source Type: research

Use of pimobendan in feline congenital heart failure.
Abstract A 6-month-old domestic shorthair cat was referred for evaluation of sudden lethargy and tachypnea following ovariohysterectomy. Upon failure of improvement with supportive care, a cardiologist identified congenital tricuspid dysplasia with signs of heart failure. Furosemide, enalapril, and pimobendan were used to reduce clinical signs and improve length and quality of life. PMID: 24293678 [PubMed - in process] (Source: The Canadian Veterinary Journal)
Source: The Canadian Veterinary Journal - December 1, 2013 Category: Veterinary Research Authors: Wainberg S Tags: Can Vet J Source Type: research

ACE inhibitor angioedema - A very late presentation.
Abstract Case study The patient, a hypertensive man, 77 years of age, presented at a local rural hospital after noticing increasing swelling of his tongue, leading to difficulty talking and then difficulty breathing. These symptoms developed over about 2 hours and he had not noted any rash. He had been on enalapril 10-20 mg for 23 years. He had also been on hydrochlorothiazide and atorvastatin for some years. He had not taken any non-steroidal anti-inflammatory drugs (NSAIDs) before the swelling developed. PMID: 24324986 [PubMed - in process] (Source: Australian Family Physician)
Source: Australian Family Physician - December 1, 2013 Category: Primary Care Authors: Howarth D Tags: Aust Fam Physician Source Type: research

Chronic vasodilation increases renal medullary PDE5A and {alpha}-ENaC through independent renin-angiotensin-aldosterone system pathways
We have previously observed that many of the renal and hemodynamic adaptations seen in normal pregnancy can be induced in virgin female rats by chronic systemic vasodilation. Fourteen-day vasodilation with sodium nitrite or nifedipine (NIF) produced plasma volume expansion (PVE), hemodilution, and increased renal medullary phosphodiesterase 5A (PDE5A) protein. The present study examined the role of the renin-angiotensin-aldosterone system (RAAS) in this mechanism. Virgin females were treated for 14 days with NIF (10 mg·kg–1·day–1 via diet), NIF with spironolactone [SPR; mineralocorticoid receptor ...
Source: AJP: Regulatory, Integrative and Comparative Physiology - November 15, 2013 Category: Physiology Authors: West, C. A., Shaw, S., Sasser, J. M., Fekete, A., Alexander, T., Cunningham, M. W., Masilamani, S. M. E., Baylis, C. Tags: Cardiovascular and Renal Integration Source Type: research

Vitamin D receptor-modulated Hsp70/AT1 expression may protect the kidneys of SHRs at the structural and functional levels.
rder L, Manucha W Abstract Previous hypertension studies have shown that low levels of vitamin D are linked to elevated renin-angiotensin system. The heat shock protein 70 regulates signaling pathways for cellular oxidative stress responses. Hsp70 has been shown to protect against angiotensin II-induced hypertension and exert a cytoprotective effect. Here, we wanted to evaluate whether the vitamin D receptor (VDR) associated with Hsp70/AT1 expression may be involved in the mechanism by which paricalcitol provides renal protection in spontaneously hypertensive rats (SHRs). One-month-old female SHRs were treated for...
Source: Cell Stress and Chaperones - November 13, 2013 Category: Cytology Authors: García IM, Altamirano L, Mazzei L, Fornés M, Cuello-Carrión FD, Ferder L, Manucha W Tags: Cell Stress Chaperones Source Type: research

Antidepressant induced recurrent hyponatremia: A case report.
cute;rez-Maciá V Abstract 1Hyponatremia is a known adverse effect of antidepressants. A review of the literature was performed in relation to one case treated in our hospital to identify risk factors and possible psychopharmacologic alternatives. A 57-year old woman with HIV and HCV suffered 4 episodes of severe hyponatremia within 5 months of treatment involving the following drugs: thiazide diuretic, venlafaxine, citalopram, olanzapine, haloperidol, enalapril and escitalopram. Risk of hyponatremia is higher in patients treated with antidepressants, especially selective serotonin reuptake inhibitors. Advan...
Source: Actas Espanolas de Psiquiatria - November 1, 2013 Category: Psychiatry Authors: Martínez-Cortés M, Ogando-Portilla N, Pecino-Esquerdo B, Pérez-Maciá V Tags: Actas Esp Psiquiatr Source Type: research

Effects of oral enalapril and verapamil on dialysis adequacy and solute clearance in chronic ambulatory peritoneal dialysis.
This study was undertaken with the aim to evaluate the effects of oral administration of Verapamil and Enalapril among continuous ambulatory peritoneal dialysis (CAPD) patients. The results of this study showed that Verapamil and Enalapril do not have any effects on glucose, creatinine, sodium, potassium and urea clearance (during the 4-h peritoneal equilibration test (PET) test). However, it was shown that Enalapril significantly increased the peritoneal urea Kt/V and caused a meaningful decrease in the diastolic and mean blood pressures. Therefore, we feel that Enalapril may be administered as an anti-hypertensive medica...
Source: Saudi Journal of Kidney Diseases and Transplantation - November 1, 2013 Category: Urology & Nephrology Authors: Atabak S, Taziki O, Argani H, Abolghasemi R, Zangneh HF, Rahmani L Tags: Saudi J Kidney Dis Transpl Source Type: research

Abstract 380: Short-term Treatment with Lercanidipine May Modulate Insuling Signalling and Oxidative Stress in Hypertensive Patients [Poster Session II]
We investigated the effects of antihypertensive treatment with two drug combinations on insulin signalling and oxidative stress.Twenty essential hypertensive patients were included in the study and treated for 4 weeks with lercanidipine orally. Then they were treated for 6 months with lercanidipine+enalapril (n=10) or lercanidipine+hydrochlorothiazide (n=10). Investigations were performed in basal condition, after 4 weeks of monotherapy with lercanidipine, and at the end of the combination treatment. Insulin signalling was evaluated in mononuclear cells by Wester-Blot. Circulating levels of C-reactive protein (CRP), proinf...
Source: Hypertension - October 30, 2013 Category: Cardiology Authors: Rossini, C., De Ciuceis, C., Flati, V., Rufo, A., Porteri, E., Di Gregorio, J., Petroboni, B., La Boria, E., Sarkar, A., Agabiti Rosei, C., Rizzoni, D., Agabiti Rosei, E. Tags: Poster Session II Source Type: research

Abstract 410: Combination Therapy With Lercanidipine and Enalapril Improves Wave Reflection in Hypertensive Patients With Metabolic Sindrome [Poster Session II]
In conclusion, the addition of LER caused the same PWV reduction as compared to HCT but greater reduction in AI in hypertensive patients with metabolic syndrome not controlled with Enalapril alone. These results indicate a positive effect of the combination with LER on wave reflection, suggesting a potential role for cardiovascular protection. (Source: Hypertension)
Source: Hypertension - October 30, 2013 Category: Cardiology Authors: Ghiadoni, L., Bruno, R. M., Stea, F., Cartoni, G., Virdis, A., Grassi, D., Ferri, C., Taddei, S. Tags: Poster Session II Source Type: research

Abstract 452: The Degree of Nephron Deficit is a Determinant of the Cardiovascular and Renal Risks Associated With a Reduced Nephron Endowment [Poster Session II]
We examined whether nephron endowment, and the degree of nephron deficit, impacts on the blood pressure and renal response to chronic angiotensin II (AngII) infusion. To address this aim we used the GDNF heterozygous mouse that, despite the same genotype, produces two distinct levels of nephron deficit due to the role of GDNF in both the initiation of kidney development and induction of nephron formation. GDNF het mice are born with either 2 small kidneys and a 30% nephron deficit (Het2K), or a single small kidney (Het1K) and a 65% nephron deficit compared to wild-type littermates (WT).Sixteen week old male GDNF WT (n=9), ...
Source: Hypertension - October 30, 2013 Category: Cardiology Authors: Kett, M. M., Makuei, L., Cai, X., Brown, R. D. Tags: Poster Session II Source Type: research

Abstract 602: Mass Spectrometry Based Characterization of Angiotensin Metabolism in ACE2 Deficient Mice Treated with RAS Blockers [Poster Session II]
The Renin-Angiotensin-System is a peptide hormone cascade being responsible for the regulation of blood pressure and fluid balance through a sophisticated signaling network. During recent years the local Renin-Angiotensin-System (RAS) moved increasingly into the focus of research as the expression of multiple angiotensin processing enzymes had been reported for tissues. Nevertheless, scientific progress in this field is hampered due to the obvious presence of technical caveats in the analysis of the local RAS, which are indicated by a tremendous variation of tissue angiotensin levels reported in the literature. Hence, in o...
Source: Hypertension - October 30, 2013 Category: Cardiology Authors: Oliver, D., Manzel, A., Stegbauer, J., Gurley, S. B., Antlanger, M., Kovarik, J., Linker, R., Saemann, M., Poglitsch, M. Tags: Poster Session II Source Type: research

Long-term effects of addition of mineralocorticoid receptor antagonist to angiotensin II receptor blocker in patients with diabetic nephropathy: a randomized clinical trial
This study was designed to assess the long-term efficacy of SPR/ARB combination in comparison with the standard ACE/ARB regimen in diabetic nephropathy. Methods In an open-label, parallel-group, single-center, randomized clinical trial (NCT01667614), 136 patients with diabetes and proteinuria, already treated with enalapril and losartan, were included. In 74 patients, ACE inhibitors were discontinued. After a wash-out period of 2 weeks, 25 mg SPR daily was initiated. The remainder of the patients (n = 62) received ACE inhibitors and ARBs as before. Patients were followed every 3 months for 18 months. During each visit, sy...
Source: Nephrology Dialysis Transplantation - October 29, 2013 Category: Urology & Nephrology Authors: Esteghamati, A., Noshad, S., Jarrah, S., Mousavizadeh, M., Khoee, S. H., Nakhjavani, M. Tags: Chronic Kidney Disease Source Type: research

Enalapril enhances the anticonvulsant activity of lamotrigine in the test of maximal electroshock.
Abstract Background: The aim of this study was to find out whether angiotensin-converting enzyme (ACE) inhibitors, enalapril and cilazapril, affect the anticonvulsant action of some second-generation antiepileptics, lamotrigine (LTG), topiramate (TPM) and oxcarbazepine (OXC). Methods: The effects of ACE inhibitors on antiepileptic drugs were examined in the mouse model of maximal electroshock. Results: Enalapril (30 mg/kg ip) potentiated the anticonvulsant action of LTG, decreasing its ED50 value from 5.3 to 3.6 mg/kg (p
Source: Pharmacological Reports - October 23, 2013 Category: Drugs & Pharmacology Authors: Lukawski K, Jakubus T, Janowska A, Raszewski G, Czuczwar SJ Tags: Pharmacol Rep Source Type: research

Enalapril Mitigates Radiation-Induced Pneumonitis and Pulmonary Fibrosis if Started 35 Days after Whole-Thorax Irradiation.
Abstract Victims of a radiological attack or nuclear accident may receive high-dose, heterogeneous exposures from radiation to the chest that lead to lung damage. Our goal is to develop countermeasures to mitigate such injuries. We used WAG/RijCmcr rats receiving 13 Gy to the whole thorax to induce pulmonary fibrosis within 210 days. The angiotensin converting enzyme (ACE) inhibitor enalapril was evaluated as a mitigator of these injuries at two doses (18 and 36 mg/m(2)/day) and 8 schedules: starting at 7, 35, 70, 105 and 140 days and continuing to 210 days or starting at 7 days and stopping at 30, 60 or 90 days a...
Source: Radiation Research - October 18, 2013 Category: Physics Authors: Gao F, Fish BL, Moulder JE, Jacobs ER, Medhora M Tags: Radiat Res Source Type: research

Endothelin-1, Oxidative Stress, and Endogenous Angiotensin II: Mechanisms of Angiotensin II Type I Receptor Autoantibody-Enhanced Renal and Blood Pressure Response During Pregnancy [Preeclampsia]
This study was designed to determine mechanisms whereby agonistic autoantibodies to the ANGII type I receptor (AT1-AA) enhance blood pressure (mean arterial pressure [MAP]) and renal vascular sensitivity to ANGII during pregnancy. First, we examined MAP and renal artery resistance index in response to chronic administration of ANGII or AT1-AA or AT1-AA+ANGII in pregnant rats compared with control pregnant rats. To examine mechanisms of heightened sensitivity in response to AT1-AA during pregnancy, we examined the role of endogenous ANGII in AT1-AA–infused pregnant rats, and that of endothelin-1 and oxidative stress i...
Source: Hypertension - October 16, 2013 Category: Cardiology Authors: Brewer, J., Liu, R., Lu, Y., Scott, J., Wallace, K., Wallukat, G., Moseley, J., Herse, F., Dechend, R., Martin, J. N., LaMarca, B. Tags: Animal models of human disease, Other hypertension Preeclampsia Source Type: research

Eplerenone Another Drug to Add to the Mix? ∗
Digoxin and diuretics have been used for centuries to treat the symptoms of heart failure. Yet, it was the addition of angiotensin-converting enzyme (ACE) inhibitors that revolutionized the management of chronic heart failure by demonstrating an astonishing 40% reduction in 6-month mortality when compared to placebo in the original CONSENSUS (Cooperative North Scandinavian Enalapril Survival Study) (1). The evolution of evidence-based therapies makes it difficult to study new treatments without established background therapy. Thus, beta-blockers were studied in patients already treated with ACE inhibitors; other drugs...
Source: Journal of the American College of Cardiology: Cardiovascular Interventions - October 15, 2013 Category: Cardiology Source Type: research

Blockade of A2B adenosine receptor reduces left ventricular dysfunction and ventricular arrhythmias 1 week after myocardial infarction in the rat model
Background: Remodeling occurs after myocardial infarction (MI), leading to fibrosis, dysfunction, and ventricular tachycardias (VTs). Adenosine via the A2B adenosine receptor (A2BAdoR) has been implicated in promoting fibrosis.Objective: To determine the effects of GS-6201, a potent antagonist of the A2BAdoR, on arrhythmogenic and functional cardiac remodeling after MI.Methods: Rats underwent ischemia-reperfusion MI and were randomized into 4 groups: control (treated with vehicle), angiotensin-converting enzyme inhibitor (treated with enalapril 1 day after MI), GS-6201-1d (treated with GS-6201 1 day after MI), GS-6201-1w (...
Source: Heart Rhythm - October 11, 2013 Category: Cardiology Authors: Hao Zhang, Hongyan Zhong, Thomas H. Everett, Emily Wilson, Roger Chang, Dewan Zeng, Luiz Belardinelli, Jeffrey E. Olgin Tags: Experimental Source Type: research

Quantification of pharmaceuticals and personal care product residues in surface and drinking water samples by SPE and LC-ESI-MS/MS
Currently, industrialized nations have faced a new problem, the contamination of water by emerging contaminants, such as pharmaceuticals and personal care products (PPCPs). A method based on solid-phase extraction (SPE) and liquid chromatography with electrospray ionization source tandem mass spectrometry was developed and validated for the determination of nimesulide, amitriptyline, enalapril, glibenclamide, haloperidol and methylparaben in water samples. In the study of SPE, a 2v5-1 fractional factorial design was used as a tool for the selection of the most significant variables in the extraction efficiency of the analy...
Source: Journal of the Brazilian Chemical Society - September 27, 2013 Category: Chemistry Source Type: research

Chronic vasodilation increases renal medullary PDE5A and {propto}ENaC through independent renin-angiotensin-aldosterone system (RAAS) pathways.
Abstract We have previously observed that many of the renal and hemodynamic adaptations seen in normal pregnancy can be induced in virgin female rats by chronic systemic vasodilation. Fourteen-day vasodilation with sodium nitrite (NaNO2) or nifedipine (NIF) produced plasma volume expansion (PVE), hemodilution and increased renal medullary phosphodiesterase 5 A (PDE5A) protein. The present study examined the role of the RAAS in this mechanism. Virgin females were treated for 14 days with NIF; 10 mg/kg/day, NIF with spironolactone (SPR; mineralocorticoid receptor (MR) blocker, 200-300 mg/kg/day), NIF with losartan (...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - September 25, 2013 Category: Physiology Authors: West CA, Shaw S, Sasser JM, Fekete A, Alexander T, Cunningham MW, Masilamani SM, Baylis C Tags: Am J Physiol Regul Integr Comp Physiol Source Type: research

Effect of NR3C2 genetic polymorphisms on the blood pressure response to enalapril treatment
Pharmacogenomics , Ahead of Print, Pages 1-8. (Source: Future Medicine: Pharmacogenomics)
Source: Future Medicine: Pharmacogenomics - September 24, 2013 Category: Genetics & Stem Cells Tags: article Source Type: research

Enalapril/Carvedilol for Prevention of Chemotherapy-Induced Heart Failure: An End to the Problem
I read with great interest the article by Bosch et al. looking at enalapril and carvedilol for prevention of chemotherapy-induced left ventricular systolic dysfunction (LVSD). (Source: Journal of the American College of Cardiology)
Source: Journal of the American College of Cardiology - September 6, 2013 Category: Cardiology Authors: Harsh Golwala Tags: Letters to the Editor Source Type: research

Enalapril and Carvedilol for Preventing Chemotherapy-Induced Left Ventricular Systolic Dysfunction
We read with great interest the article by Bosch et al. . We congratulate the authors for their work, which sheds new light on the potential for preventing cardiotoxic effects of anticancer therapies. However, there are a few aspects that, in our opinion, need clarification. (Source: Journal of the American College of Cardiology)
Source: Journal of the American College of Cardiology - September 6, 2013 Category: Cardiology Authors: Paolo Spallarossa, Marco Guerrini, Eleonora Arboscello, Vera Sicbaldi Tags: Letters to the Editor Source Type: research

Reply: Enalapril and Carvedilol for Preventing Chemotherapy-Induced Left Ventricular Systolic Dysfunction in Patients With Malignant Hemopathies
We thank Dr. Golwala and Dr. Spallarossa and colleagues for their interest in our study. Both ask about the lack of association found in our study between troponin elevation and benefit from pharmacological intervention. The value of troponins to predict left ventricular systolic dysfunction (LVSD) has been reported with anthracyclines but not with other drugs . However, we do not believe that our results are contradictory to those of Cardinale et al. ; differences in the patient population, intensity and type of chemotherapy, and protocol design of both studies may account for their different results. Cardi...
Source: Journal of the American College of Cardiology - September 6, 2013 Category: Cardiology Authors: Xavier Bosch, Marta Sitges, Montserrat Rovira, José Tomás Ortiz-Pérez, Jordi Esteve Tags: Letters to the Editor Source Type: research

Beneficial Influence of Carvedilol on Urologic Indices in Patients With Hypertension and Benign Prostatic Hyperplasia: Results of a Randomized, Crossover Study
Objective: To assess the influence of carvedilol, an α- and β-blocker, on lower urinary tract symptoms (LUTS) and urine flow in hypertensive patients with benign prostatic hyperplasia (BPH).Methods: Fifty men were included in this double blind crossover study with placebo. After initial screening, participants were randomized to the carvedilol or the enalapril group, with cross over after 3 months. Doses of both drugs were uptitrated or additional therapy was introduced to ensure normal control of blood pressure (BP). Urologic assessment included uroflowmetry (average [Qavg] and maximum urinary flow rate [Q...
Source: Urology - September 1, 2013 Category: Urology & Nephrology Authors: Jacek Lewandowski, Maciej Sinski, Bartosz Symonides, Jerzy Korecki, Krzysztof Rogowski, Jacek Judycki, Artur Sieczych, Olga Możeńska, Zbigniew Gaciong Tags: Prostatic Diseases and Male Voiding Dysfunction Source Type: research

Acquired Gerbode defect and third‐degree atrioventricular block secondary to vehicular trauma in a dog
Abstract ObjectiveTo describe a case of traumatically acquired left ventricular to right atrial communication (Gerbode defect), atrial septal defect (ASD), and third‐degree atrioventricular block (AVB) necessitating permanent pacemaker placement in a dog. Case SummaryA 1.5‐year‐old neutered male Newfoundland dog was struck by a car and was referred for further evaluation and treatment of hemoabdomen. Persistent third‐degree AVB, a right‐sided cardiac murmur and right‐sided congestive heart failure (CHF) were identified, and echocardiographic examination revealed a type‐A Gerbode defect and ASD. Pimobendan, fu...
Source: Journal of Veterinary Emergency and Critical Care - September 1, 2013 Category: Veterinary Research Authors: Suzanne M. Cunningham, Kathleen J. Lindsey, John E. Rush Tags: Case Report Source Type: research

Beneficial Influence of Carvedilol on Urologic Indices in Patients With Hypertension and Benign Prostatic Hyperplasia: Results of a Randomized, Crossover Study
Objective: To assess the influence of carvedilol, an α- and β-blocker, on lower urinary tract symptoms (LUTS) and urine flow in hypertensive patients with benign prostatic hyperplasia (BPH).Methods: Fifty men were included in this double blind crossover study with placebo. After initial screening, participants were randomized to the carvedilol or the enalapril group, with cross over after 3 months. Doses of both drugs were uptitrated or additional therapy was introduced to ensure normal control of blood pressure (BP). Urologic assessment included uroflowmetry (average [Qavg] and maximum urinary flow rate [Q...
Source: Urology - August 28, 2013 Category: Urology & Nephrology Authors: Jacek Lewandowski, Maciej Sinski, Bartosz Symonides, Jerzy Korecki, Krzysztof Rogowski, Jacek Judycki, Artur Sieczych, Olga Możeńska, Zbigniew Gaciong Tags: Prostatic Diseases and Male Voiding Dysfunction Source Type: research

Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF)
Aims Although the focus of therapeutic intervention has been on neurohormonal pathways thought to be harmful in heart failure (HF), such as the renin–angiotensin–aldosterone system (RAAS), potentially beneficial counter-regulatory systems are also active in HF. These promote vasodilatation and natriuresis, inhibit abnormal growth, suppress the RAAS and sympathetic nervous system, and augment parasympathetic activity. The best understood of these mediators are the natriuretic peptides which are metabolized by the enzyme neprilysin. LCZ696 belongs to a new class of drugs, the angiotensin receptor neprilysin inhib...
Source: European Journal of Heart Failure - August 19, 2013 Category: Cardiology Authors: McMurray, J. J. V., Packer, M., Desai, A. S., Gong, J., Lefkowitz, M. P., Rizkala, A. R., Rouleau, J., Shi, V. C., Solomon, S. D., Swedberg, K., Zile, M. R., on behalf of the PARADIGM-HF Committees and Investigators Tags: STUDY DESIGN Source Type: research

The direct renin inhibitor aliskiren localizes and persists in rat kidneys.
Abstract The aims of this study were to 1) determine whether renal localization of aliskiren and its anti-hypertensive and renoprotective effects persist after stopping administration of the drug, and 2) define the renal localization of aliskiren by light microscopy autoradiography. Hypertensive double transgenic rats (dTGR) overexpressing genes for human renin and angiotensinogen were treated with aliskiren (3 mg/kg/day sc; osmotic minipumps) or enalapril (18mg/L in drinking water). After 2 weeks treatment dTGR were assigned to either continued treatment with aliskiren ("continued"), or to cessation of ...
Source: Am J Physiol Renal P... - August 7, 2013 Category: Urology & Nephrology Authors: Feldman DL, Jin L, Xuan H, Persohn E, Zhou W, Schuetz H, Park JK, Mueller DN, Luft FC Tags: Am J Physiol Renal Physiol Source Type: research

Risk of hyperkalemia in patients with moderate chronic kidney disease initiating angiotensin converting enzyme inhibitors or angiotensin receptor blockers: a randomized study
Conclusions: Disturbances in potassium balance upon treatment with either olmesartan or enalapril are frequent and without differences between groups. The follow-up of these patients should include control of potassium levels, at least after the first week and the first and second month after initiating treatment.Trial registration: The trial EudraCT "2008-002191-98". (Source: BMC Research Notes)
Source: BMC Research Notes - August 1, 2013 Category: Research Authors: Eugenia EspinelJorge JovenIván GilPilar SuñéBerta RenedoJoan FortDaniel Serón Source Type: research

The effects of antihypertensive drugs on bone mineral density in ovariectomized mice.
Abstract The effects of several antihypertensive drugs on bone mineral density (BMD) and micro-architectural changes in ovariectomized (OVX) mice were investigated. Eight-week-old female C57/BL6 mice were used for this study. Three days after ovariectomy, mice were treated intraperitoneally with nifedipine (15 mg/kg), telmisartan (5 mg/kg), enalapril (20 mg/kg), propranolol (1 mg/kg) or hydrochlorothiazide (12.5 mg/kg) for 35 consecutive days. Uterine atrophy of all mice was confirmed to evaluate estrogen deficiency state. BMD and micro-architectural analyses were performed on tibial proximal ends by micro-compute...
Source: J Korean Med Sci - August 1, 2013 Category: Journals (General) Authors: Kang KY, Kang Y, Kim M, Kim Y, Yi H, Kim J, Jung HR, Park SH, Kim HY, Ju JH, Hong YS Tags: J Korean Med Sci Source Type: research

Effect of Stearic Acid on Enalapril Stability and Dissolution from Multiparticulate Solid Dosage Forms.
This study evaluated the effect of stearic acid (SA) on enalapril stability in microcrystalline cellulose (MCC) pellets containing EM or NaE. MCC pellets containing SA were prepared by the extrusion-spheronization technique and characterized. Enalapril stability and dissolution were then evaluated. DPK and enalaprilate formation were reduced by the addition of SA in pellets containing EM. The overall enalapril degradation in these formulations was lower when compared with pellets containing EM or even NaE prepared without SA. The immediate-release characteristic was maintained by the addition of 5% crospovidone to all the ...
Source: AAPS PharmSciTech - July 30, 2013 Category: Drugs & Pharmacology Authors: Cunha TA, Serpa RC, de Oliveira AP, Nasser LN, de Freitas LA, Taveira SF, Diniz DG, Lima EM, Marreto RN Tags: AAPS PharmSciTech Source Type: research

Increase in Lipophilicity of Enalaprilat by Complexation with Copper(II) or Zinc(II) Ions.
Abstract Enalaprilat (H2L), which is the active metabolite of the pro-drug enalapril, is an angiotensin-converting enzyme inhibitor. Some side effects such as neurodegeneration and taste disorder can be related to copper or zinc deficiency, which would be caused by the metal complex formation of dianionic elalaprilat (L(2-)). For a better understanding of this phenomenon, we investigated the solution species of enalaprilat in the presence of copper(II) or zinc(II) ions by pH titration analysis with I = 0.10 M (NaCl) at 25℃. The 1:1 complex formation constants (KML = [ML]/[M(2+)][L(2-)] M(-1)) of 10(7.4) for CuL ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 30, 2013 Category: Drugs & Pharmacology Authors: Fujioka H, Hieda Y, Kuramoto Y, Konishi K, Kinoshita-Kikuta E, Kinoshita E, Koike T Tags: Yakugaku Zasshi Source Type: research

Enalapril versus losartan for adults with chronic kidney disease: a systematic review and meta‐analysis
ConclusionEnalapril has similar effects to losartan on systemic blood pressure, renal function and serum UA in patients with CKD, but carries a higher risk of dry cough. Larger trials are required to evaluate the effects of these medications on clinical outcomes. (Source: Nephrology)
Source: Nephrology - July 19, 2013 Category: Urology & Nephrology Authors: Yuan‐Mei He, Li Feng, Dong‐Mei Huo, Zhen‐Hua Yang, Yun‐Hua Liao Tags: Original Article Source Type: research

Nanoparticle PET-CT Detects Rejection and Immunomodulation in Cardiac Allografts [Original Articles]
Background— Macrophages predominate among the inflammatory cells in rejecting allografts. These innate immune cells, in addition to allospecific T cells, can damage cardiomyocytes directly. Methods and Results— We explored whether sensitive positron emission tomography–computed tomography (PET-CT) imaging of macrophages-avid nanoparticles detects rejection of heart allografts in mice. In addition, we used the imaging method to follow the immunomodulatory impact of angiotensin-converting enzyme inhibitor therapy on myeloid cells in allografts. Dextran nanoparticles were derivatized with the PET isotope co...
Source: Circulation: Cardiovascular Imaging - July 16, 2013 Category: Radiology Authors: Ueno, T., Dutta, P., Keliher, E., Leuschner, F., Majmudar, M., Marinelli, B., Iwamoto, Y., Figueiredo, J.-L., Christen, T., Swirski, F. K., Libby, P., Weissleder, R., Nahrendorf, M. Tags: Nuclear cardiology and PET Original Articles Source Type: research

PKPD modelling of the interrelationship between mean arterial BP, cardiac output and total peripheral resistance in conscious rats
Conclusions and ImplicationsA system‐specific model characterizing the interrelationship between BP, CO and TPR was obtained, which can be used to quantify and predict the cardiovascular effects of a drug and to elucidate the MoA for novel compounds. Ultimately, the proposed PKPD model could be used to predict the effects of a particular drug on BP in humans based on preclinical data. (Source: British Journal of Pharmacology)
Source: British Journal of Pharmacology - July 12, 2013 Category: Drugs & Pharmacology Authors: N Snelder, B A Ploeger, O Luttringer, D F Rigel, R L Webb, D Feldman, F Fu, M Beil, L Jin, D R Stanski, M Danhof Tags: Research Paper Source Type: research

Contributions of Leukocyte Angiotensin-Converting Enzyme to Development of Atherosclerosis.
CONCLUSIONS: ACE mediates angiotensin I-induced atherosclerosis, and ACE expression in leukocytes modestly contributes to atherosclerotic development in hypercholesterolemic mice. PMID: 23846498 [PubMed - as supplied by publisher] (Source: Arteriosclerosis, Thrombosis and Vascular Biology)
Source: Arteriosclerosis, Thrombosis and Vascular Biology - July 11, 2013 Category: Cardiology Authors: Chen X, Lu H, Zhao M, Tashiro K, Cassis LA, Daugherty A Tags: Arterioscler Thromb Vasc Biol Source Type: research

Centrally Mediated Erectile Dysfunction in Rats with Type 1 Diabetes: Role of Angiotensin II and Superoxide
This study aims to determine the contribution of angiotensin (ANG) II in the dysfunction of central N‐methyl‐D‐aspartic acid (NMDA)‐ and nitric oxide (NO)‐induced erectile responses in streptozotocin‐induced type 1 diabetic (T1D) rats. MethodsThree weeks after streptozotocin injections, rats were randomly treated with the angiotensin‐converting enzyme inhibitor‐enalapril, or the ANG II type 1 receptor blocker, losartan, or the superoxide dismutase mimetic, tempol, or vehicle via chronic intracerebroventricular infusion by osmotic mini‐pump for 2 weeks. Main Outcome MeasureCentral NMDA receptor stimulation...
Source: The Journal of Sexual Medicine - July 10, 2013 Category: Sexual Medicine Authors: Hong Zheng, Xuefei Liu, Kaushik P. Patel Tags: Original Research Source Type: research

Inhibition of the renin-angiotensin system does not reduce platelet activity at rest or during stress in hypertension
Objectives:We investigated the influence of angiotensin receptor blockade and angiotensin-converting enzyme inhibition on stress-induced platelet activation in hypertensive patients. Secondary aims were effects on inflammation, coagulation, and endothelial function. Methods:Following a 4-week placebo period, 25 hypertensive patients entered a double-blind, crossover study comparing enalapril (20 mg once daily) and losartan (100 mg once daily) treatment (each for 8 weeks). Patients were studied at rest and after a standardized exercise test. Results:Mean arterial pressure was reduced from 119 ± 2 to 104 &pl...
Source: Journal of Hypertension - July 8, 2013 Category: Cardiology Tags: ORIGINAL PAPERS: Therapeutic aspects Source Type: research

Eplerenone: Another Drug to Add to the Mix?∗
Digoxin and diuretics have been used for centuries to treat the symptoms of heart failure. Yet, it was the addition of angiotensin-converting enzyme (ACE) inhibitors that revolutionized the management of chronic heart failure by demonstrating an astonishing 40% reduction in 6-month mortality when compared to placebo in the original CONSENSUS (Cooperative North Scandinavian Enalapril Survival Study) . The evolution of evidence-based therapies makes it difficult to study new treatments without established background therapy. Thus, beta-blockers were studied in patients already treated with ACE inhibitors; other drugs su...
Source: Journal of the American College of Cardiology - June 28, 2013 Category: Cardiology Authors: Bradley A. Bart, Sarah Nelson Tags: Heart Failure: Editorial Comment Source Type: research

Assessing heterogeneity of treatment effect in a clinical trial with the proportional interactions model
We describe methods for constructing a confidence interval for the proportionality parameter. In simulation studies, we show that our modified Bonferroni adjustment controls familywise error and has greater power to detect proportional interactions compared with multiplcity‐corrected subgroup analyses. We demonstrate our methodology by using the Studies of Left Ventricular Dysfunction Treatment trial, a placebo‐controlled randomized clinical trial of the efficacy of enalapril to reduce the risk of death or hospitalization in chronic heart failure patients. An R package called anoint is available for implementing the pr...
Source: Statistics in Medicine - June 22, 2013 Category: Statistics Authors: Stephanie A. Kovalchik, Ravi Varadhan, Carlos O. Weiss Tags: Research Article Source Type: research

Enalapril and Carvedilol for Preventing Chemotherapy-Induced Left Ventricular Systolic Dysfunction in Patients With Malignant Hemopathies The OVERCOME Trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies)
This study sought to evaluate the efficacy of enalapril and carvedilol to prevent chemotherapy-induced left ventricular systolic dysfunction (LVSD) in patients with hematological malignancies.BackgroundCurrent chemotherapy may induce LVSD. Angiotensin-converting enzyme inhibitors and beta-blockers prevent LVSD in animal models of anthracycline-induced cardiomyopathy.MethodsIn this randomized, controlled study, 90 patients with recently diagnosed acute leukemia (n = 36) or patients with malignant hemopathies undergoing autologous hematopoietic stem cell transplantation (HSCT) (n = 54) and without LVSD were ra...
Source: Journal of the American College of Cardiology: Cardiovascular Interventions - June 4, 2013 Category: Cardiology Source Type: research

Cardiovascular autonomic modulation by nitric oxide synthases accounts for the augmented enalapril-evoked hypotension in ethanol-fed female rats
In this study, we investigated the role of nitric oxide synthase (NOS) isoforms in the enhanced enalapril-evoked hypotension in ethanol-fed female rats by examining the effect of the selective inhibitors of eNOS [N5-(1-iminoethyl)-l-ornithine; l-NIO], nNOS (Nω-propyl-l-arginine; NPLA), or iNOS (1400W) inhibition on the cardiovascular effects of enalapril in ethanol- (5% w/v) fed rats and in their pair-fed controls. In liquid diet-fed control rats, enalapril- (10 mg/kg) evoked hypotension was abolished by l-NIO (20 mg/kg), but not by NPLA (1 mg/kg) or 1400W (5 mg/kg), suggesting a preferential role...
Source: Alcohol - May 23, 2013 Category: Addiction Authors: Mahmoud M. El-Mas, Abdel A. Abdel-Rahman Source Type: research

Therapeutic substitution post‐patent expiry: the cases of ace inhibitors and proton pump inhibitors
This paper examines whether there is a switch in total (originator and generic) consumption after generic entry from molecules that face generic competition towards other molecules of the same class, which are still in‐patent. Data from six European countries for the time period 1991 to 2006 are used to study the cases of angiotensin‐converting enzyme inhibitors and proton pump inhibitors. Empirical evidence shows that patent expiry of captopril and enalapril led to a switch in total (off‐patent originator and generic) consumption towards other in‐patent angiotensin‐converting enzyme inhibitors, whereas patent ex...
Source: Health Economics - May 21, 2013 Category: Health Management Authors: Sotiris Vandoros Tags: Health Economics Letter Source Type: research

Abstract 232: Parenteral Antihypertensive Use on the First Day of Hospitalization after Acute Ischemic Stroke: A US Population Study [Poster Session II]
Introduction: Elevated blood pressure (BP) is associated with increased risk of neurologic decline and poor outcome in acute ischemic stroke (AIS). The American Stroke Association (ASA) recommends antihypertensive (AH) therapy if BP is>220/120 mmHg, with a goal of 15-25% reduction in the first 24 hours. In thrombolytic candidates, BP should be maintained ≤185/110 mmHg for 24 hours after rt-PA. Labetalol and nicardipine are the recommended parenteral (IV) agents. We sought to characterize the use of IV AHs in the first 24 hours after AIS admission, stratified by treatment with rt-PA.Methods: This analysis utilized the...
Source: Circulation: Cardiovascular Quality and Outcomes - May 15, 2013 Category: Cardiology Authors: Wang, Y., McDonough, E., Adeoye, O., LaPensee, K., Crothers, T. C., Kleindorfer, D. Tags: Poster Session II Source Type: research

Superior renoprotective effects of the combination of breviscapine with enalapril and its mechanism in diabetic rats
Abstract: Breviscapine is a flavonoid extracted from a Chinese herb Erigeron breviscapus, previously it was shown that treatment with breviscapine attenuated renal injury in the diabetic rats. The purpose of this study was to investigate whether breviscapine combined with enalapril (an ACE inhibitor) have superior renoprotective effects against diabetic nephropathy. Rats were randomly separated into five groups: control, diabetes, diabetes treated with enalapril, diabetes treated with breviscapine, or diabetes treated with combined enalapril with breviscapine. Twenty-four hours urinary AER and the levels of 3-NT in renal t...
Source: Phytomedicine - May 13, 2013 Category: Drugs & Pharmacology Authors: Xing-Xin Xu, Wei Zhang, Pei Zhang, Xiang-Ming Qi, Yong-Gui Wu, Ji-Jia Shen Tags: Diabetes and endocrinology Source Type: research

Sex differences in angiotensin-converting enzyme modulation of Ang (1-7) levels in normotensive WKY rats.
Abstract BACKGROUND: Levels of the vasodilatory peptide angiotensin (Ang) (1-7) have been reported to be greater in females than in males, although the molecular mechanism responsible for this is unknown. Angiotensin-converting enzyme (ACE), ACE2, and neprilysin are key enzymes regulating Ang (1-7) formation. We conducted a study to determine the effect of sex on the activities of ACE, ACE2, and neprilysin in the kidneys of normotensive rats. We hypothesized that greater ACE2 or neprilysin activity in females would result in enhanced Ang (1-7) formation as compared with that in males. METHODS: We measured the...
Source: American Journal of Hypertension - May 1, 2013 Category: Cardiology Authors: Bhatia K, Zimmerman MA, Sullivan JC Tags: Am J Hypertens Source Type: research