Angiotensin-(1-7) attenuates the development of heart failure after myocardial infarction in rats.
BACKGROUND
The renin-angiotensin system (RAS) is a key player in the progression of heart failure. Angiotensin-(1-7) is thought to modulate the activity of the RAS. Furthermore, this peptide may play a part in the beneficial effects of angiotensin-converting enzyme inhibitors in cardiovascular disease. We assessed the effects of angiotensin-(1-7) on the progression of heart failure.


RESULTS
Male Sprague-Dawley rats underwent either coronary ligation or sham surgery. Two weeks after induction of myocardial infarction, intravenous infusion of angiotensin-(1-7) (24 microg/kg per hour) or saline was started by minipump. After 8 weeks of treatment, hemodynamic parameters were measured, endothelial function was assessed in isolated aortic rings, and plasma angiotensin-(1-7) levels were determined. Myocardial infarction resulted in a significant deterioration of left ventricular systolic and diastolic pressure, dP/dt, and coronary flow. Raising plasma levels 40-fold, angiotensin-(1-7) infusion attenuated this impairment to a nonsignificant level, markedly illustrated by a 40% reduction in left ventricular end-diastolic pressure. Furthermore, angiotensin-(1-7) completely preserved aortic endothelial function, whereas endothelium-dependent relaxation in aortas of saline-treated infarcted rats was significantly decreased.


CONCLUSIONS
Angiotensin-(1-7) preserved cardiac function, coronary perfusion, and aortic endothelial function in a rat model for heart failure.
Loot
Annemarieke E
AE
Department of Clinical Pharmacology, University of Groningen, The Netherlands. a.e.loot@med.rug.nl
Roks
Anton J M
AJ
Henning
Robert H
RH
Tio
René A
RA
Suurmeijer
Albert J H
AJ
Boomsma
Frans
F
van Gilst
Wiek H
WH
D000803:Angiotensin I / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D003326:Coronary Circulation / Q000187:drug effects; D046508:Culture Techniques; D004730:Endothelium, Vascular / Q000503:physiopathology; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D006439:Hemodynamics; D007262:Infusions, Intravenous; D008297:Male; D009203:Myocardial Infarction / Q000150:complications*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects
D010446:Peptide Fragments; D000803:Angiotensin I; C118790:angiotensin I (1-7)