title: The specific mineralocorticoid receptor blocker eplerenone attenuates left ventricular remodeling in mice lacking the gene encoding guanylyl cyclase-A.
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 remodeling in GC-A KO mice. In conclusion, eplerenone attenuates cardiac remodeling in GC-A KO mice, most likely in a blood pressure-independent manner, which suggests that signaling downstream of MR is involved in the ventricular remodeling of GC-A KO mice.
authors: First Department of Internal Medicine, Nara Medical University, Nara, Japan.
authors: Qingfen
authors: Q
authors: Zhang
authors: Yoshihiko
authors: Y
authors: Saito
authors: Noriyuki
authors: N
authors: Naya
authors: Keiichi
authors: K
authors: Imagawa
authors: Satoshi
authors: S
authors: Somekawa
authors: Hiroyuki
authors: H
authors: Kawata
authors: Yukiji
authors: Y
authors: Takeda
authors: Shiro
authors: S
authors: Uemura
authors: Ichiro
authors: I
authors: Kishimoto
authors: Kazuwa
authors: K
authors: Nakao
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000502:physiology; D000077545:Eplerenone; D006162:Guanylate Cyclase / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013599:Systole / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase