Document Type
Article
Publication Date
2-1-2007
Publication Title
American Journal of Physiology. Heart and Circulatory Physiology
ISSN
0363-6135
Volume
292
Issue/No.
2
First Page
H736
Last Page
42
Abstract
Cardiac remodeling, which typically results from chronic hypertension or following an acute myocardial infarction, is a major risk factor for the development of heart failure and, ultimately, death. The renin-angiotensin system (RAS) has previously been established to play an important role in the progression of cardiac remodeling, and inhibition of a hyperactive RAS provides protection from cardiac remodeling and subsequent heart failure. Our previous studies have demonstrated that overexpression of angiotensin-converting enzyme 2 (ACE2) prevents cardiac remodeling and hypertrophy during chronic infusion of angiotensin II (ANG II). This, coupled with the knowledge that ACE2 is a key enzyme in the formation of ANG-(1-7), led us to hypothesize that chronic infusion of ANG-(1-7) would prevent cardiac remodeling induced by chronic infusion of ANG II. Infusion of ANG II into adult Sprague-Dawley rats resulted in significantly increased blood pressure, myocyte hypertrophy, and midmyocardial interstitial fibrosis. Coinfusion of ANG-(1-7) resulted in significant attenuations of myocyte hypertrophy and interstitial fibrosis, without significant effects on blood pressure. In a subgroup of animals also administered [d-Ala(7)]-ANG-(1-7) (A779), an antagonist to the reported receptor for ANG-(1-7), there was a tendency to attenuate the antiremodeling effects of ANG-(1-7). Chronic infusion of ANG II, with or without coinfusion of ANG-(1-7), had no effect on ANG II type 1 or type 2 receptor binding in cardiac tissue. Together, these findings indicate an antiremodeling role for ANG-(1-7) in cardiac tissue, which is not mediated through modulation of blood pressure or altered cardiac angiotensin receptor populations and may be at least partially mediated through an ANG-(1-7) receptor.
NSUWorks Citation
Grobe, Justin L.; Mecca, Adam P.; Lingis, Melissa; Shenoy, Vinayak; Bolton, Tonya A.; Machado, Juline M.; Speth, Robert C.; Raizada, Mohan K.; and Katovich, Michael J., "Prevention of angiotensin II-induced cardiac remodeling by angiotensin-(1-7)" (2007). HPD Articles. 64.
https://nsuworks.nova.edu/hpd_facarticles/64
ORCID ID
0000-0002-6434-2195
DOI
10.1152/ajpheart.00937.2006
Copyright
Copyright © 2007 by the American Physiological Society
