Chronic angiotensin-(1-7) prevents cardiac fibrosis in DOCA-salt model of hypertension.
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.
Grobe
Justin L
JL
Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
Mecca
Adam P
AP
Mao
Haoyu
H
Katovich
Michael J
MJ
D000803:Angiotensin I / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006332:Cardiomegaly / Q000139:chemically induced / Q000517:prevention & control; D003094:Collagen / Q000378:metabolism; D003331:Coronary Vessels / Q000473:pathology; D003900:Desoxycorticosterone; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis; D006331:Heart Diseases / Q000473:pathology / Q000517:prevention & control*; D006973:Hypertension / Q000139:chemically induced* / Q000150:complications*; D008297:Male; D010446:Peptide Fragments / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling / Q000187:drug effects
D010446:Peptide Fragments; D003900:Desoxycorticosterone; D003094:Collagen; D000803:Angiotensin I; C118790:angiotensin I (1-7)