Faculty Collaboration Database

Chronic angiotensin-(1-7) prevents cardiac fibrosis in DOCA-salt model of hypertension. Am J Physiol Heart Circ Physiol 2006 Jun;290(6):H2417-23

Date

01/18/2006

Pubmed ID

16415071

DOI

10.1152/ajpheart.01170.2005

Scopus ID

2-s2.0-33744910056 (requires institutional sign-in at Scopus site)   184 Citations

Abstract

Cardiac remodeling is a hallmark hypertension-induced pathophysiology. In the current study, the role of the angiotensin-(1-7) fragment in modulating cardiac remodeling was examined. Sprague-Dawley rats underwent uninephrectomy surgery and were implanted with a deoxycorticosterone acetate (DOCA) pellet. DOCA animals had their drinking water replaced with 0.9% saline solution. A subgroup of DOCA-salt animals was implanted with osmotic minipumps, which delivered angiotensin-(1-7) chronically (100 ng.kg(-1).min(-1)). Control animals underwent sham surgery and were maintained on normal drinking water. Blood pressure was measured weekly with the use of the tail-cuff method, and after 4 wk of treatment, blood pressure responses to graded doses of angiotensin II were determined by direct carotid artery cannulation. Ventricle size was measured, and cross sections of the heart ventricles were paraffin embedded and stained using Masson's Trichrome to measure interstitial and perivascular collagen deposition and myocyte diameter. DOCA-salt treatment caused significant increases in blood pressure, cardiac hypertrophy, and myocardial and perivascular fibrosis. Angiotensin-(1-7) infusion prevented the collagen deposition effects without any effect on blood pressure or cardiac hypertrophy. These results indicate that angiotensin-(1-7) selectively prevents cardiac fibrosis independent of blood pressure or cardiac hypertrophy in the DOCA-salt model of hypertension.

Author List

Grobe JL, Mecca AP, Mao H, Katovich MJ

Author

Justin L. Grobe PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Angiotensin I
Animals
Blood Pressure
Cardiomegaly
Collagen
Coronary Vessels
Desoxycorticosterone
Dose-Response Relationship, Drug
Fibrosis
Heart Diseases
Hypertension
Male
Peptide Fragments
Rats
Rats, Sprague-Dawley
Ventricular Remodeling