The specific mineralocorticoid receptor blocker eplerenone attenuates left ventricular remodeling in mice lacking the gene encoding guanylyl cyclase-A

Hypertension Research : Official Journal of the Japanese Society of Hypertension
Qingfen ZhangKazuwa Nakao

Abstract

Mineralocorticoid receptor (MR) blockers attenuate cardiac remodeling in experimental models of heart failure, myocardial infarction and pressure-overload, in which the renin-angiotensin-aldosterone system is activated. Mice lacking the gene encoding guanylyl cyclase-A (GC-A), a common receptor for atrial and brain natriuretic peptide (ANP and BNP, respectively), show marked cardiac hypertrophy and fibrosis, which are almost completely inhibited by both genetic and pharmacological blockade of type 1 angiotensin II receptors. However, the effect of eplerenone, a specific MR blocker, on cardiac remodeling in GC-A knockout (GC-A KO) mice remains unknown. Male 12-week-old GC-A KO mice were assigned to control, eplerenone and hydralazine groups (n=6-7/group). Treatment with eplerenone at a dose of 100 mg/kg body weight/d reduced heart weight/body weight ratios, interstitial fibrosis and blood pressure to levels similar to those seen in wild type mice, in association with reduced transcription of atrial natriuretic peptide, brain natriuretic peptide, transforming growth factor-beta1, collagen I and collagen III. Although hydralazine (5 mg/kg body weight/d) exerted a similar effect on blood pressure, it did not inhibit the cardiac rem...Continue Reading

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Citations

Jun 16, 2011·Canadian Journal of Physiology and Pharmacology·Yoshihiko SaitoKazuwa Nakao
Aug 11, 2010·The Journal of Clinical Investigation·Michael G UsherRichard M Mortensen
Oct 9, 2012·Trends in Endocrinology and Metabolism : TEM·B Julie He, Mark E Anderson
Oct 22, 2009·Clinical and Experimental Pharmacology & Physiology·Kailash N Pandey, Elangovan Vellaichamy
Oct 5, 2010·Journal of cardiology·Yoshihiko Saito
Nov 9, 2016·Journal of Neuromuscular Diseases·Jeovanna LoweJill A Rafael-Fortney
Mar 21, 2009·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Yoshiyu Takeda
May 2, 2020·Circulation. Heart Failure·João Pedro FerreiraPatrick Rossignol

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