title: Prevention of angiotensin II-induced cardiac remodeling by angiotensin-(1-7).
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.
authors.affiliation: Department of Pharmacodynamics, University of Florida, Gainesville, FL 32610-0487, USA.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Grobe
authors.forename: Adam P
authors.initials: AP
authors.lastname: Mecca
authors.forename: Melissa
authors.initials: M
authors.lastname: Lingis
authors.forename: Vinayak
authors.initials: V
authors.lastname: Shenoy
authors.forename: Tonya A
authors.initials: TA
authors.lastname: Bolton
authors.forename: Juline M
authors.initials: JM
authors.lastname: Machado
authors.forename: Robert C
authors.initials: RC
authors.lastname: Speth
authors.forename: Mohan K
authors.initials: MK
authors.lastname: Raizada
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Katovich
mesh_terms: D000704:Analysis of Variance; D000803:Angiotensin I / Q000378:metabolism* / Q000494:pharmacology; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D004195:Disease Models, Animal; D005355:Fibrosis; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000097:blood; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: C092006:7-Ala-angiotensin (1-7); D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043562:Receptors, G-Protein-Coupled; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7)