Chronic administration of angiotensin-(1-7) attenuates pressure-overload left ventricular hypertrophy and fibrosis in rats.
OBJECTIVE
To test the hypothesis that chronic administration of angiotensin-(1-7) [Ang-(1-7)] attenuates cardiac hypertrophy in rats in vivo.


METHODS
Coarctation of the suprarenal abdominal aorta was performed in 41 8-week-old male Sprague Dawley rats. Twenty-four hours after the operation, osmotic minipumps were surgically implanted subcutaneously in the rats, which were randomly divided into 3 groups, including a sham-operation group (n=15) receiving infusion with normal saline, a suprarenal aortic coarctation group (n=12), and a suprarenal aortic coarctation group (n=14) with Ang-(1-7) treatment at the dose of 25 mug x kg(-1) x h(-1). Four weeks later, the systolic and diastolic blood pressures were measured and the left ventricular mass index (LVMI, mg/g) was calculated from the ratio of left ventricular weight to body weight. The concentrations of Ang II in the plasma and myocardium were measured by radioimmunoassay, and myocardial interstitial collagen volume fraction (ICVF) was determined by quantitative morphometry of the sections with Picrosirius red staining using an automated image analyzer.


RESULTS
Suprarenal abdominal aortic coarctation induced a significant increase in carotid artery systolic and diastolic blood pressure, heart weight, LVMI, ICVF, and the concentration of Ang II in the myocardium (P<0.01). Chronic administration of Ang-(1-7) attenuated the increase in the heart weight, LVMI, ICVF and left ventricular diastolic end pressure (LVEDP) caused by suprarenal abdominal aortic coarctation (P<0.05). Ang-(1-7) also increased the formerly decreased maximum left ventricular pressure reduction rate (-dP/dt(max)) (P<0.05), but had no effect on blood pressure and the concentration of Ang II in the myocardium. No difference was noted in plasma concentration of Ang II between the 3 groups.


CONCLUSIONS
Ang-(1-7) attenuates cardiac hypertrophy and fibrosis and preserved the impaired left ventricular function induced by left ventricular pressure-overload in rats. These effects are not associated with the changes in the concentrations of Ang II in the left ventricular myocardium and plasma.
Wang
Li-jun
LJ
Department of Cardiology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China. wanglj63@163.com
He
Jian-gui
JG
Ma
Hong
H
Cai
Yi-ming
YM
Liao
Xin-xue
XX
Zeng
Wu-tao
WT
Liu
Jun
J
Wang
Li-chun
LC
D000803:Angiotensin I / Q000008:administration & dosage*; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001017:Aortic Coarctation / Q000150:complications; D001794:Blood Pressure / Q000187:drug effects; D005355:Fibrosis; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects
D000959:Antihypertensive Agents; D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7)