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Angiotensin-(1-7) attenuates the development of heart failure after myocardial infarction in rats
Annemarieke E Loot1, Anton J M Roks, Robert H Henning
1Department of Clinical Pharmacology, University of Groningen, The Netherlands. a.e.loot@med.rug.nl
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.
Methods And 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.
Insights
Angiotensin-(1-7) peptide significantly improved heart function and blood vessel health in a rat model of heart failure. This peptide offers potential therapeutic benefits for cardiovascular disease progression.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Renal Physiology
Background:
- The renin-angiotensin system (RAS) critically influences heart failure progression.
- Angiotensin-(1-7) is a peptide that may modulate RAS activity and contribute to the benefits of ACE inhibitors in cardiovascular disease.
Purpose of the Study:
- To investigate the effects of angiotensin-(1-7) on the progression of heart failure.
Main Methods:
- Male Sprague-Dawley rats underwent coronary ligation or sham surgery.
- Intravenous infusion of angiotensin-(1-7) or saline was administered for 8 weeks post-myocardial infarction.
- Hemodynamic parameters, aortic endothelial function, and plasma angiotensin-(1-7) levels were assessed.
Main Results:
- Angiotensin-(1-7) infusion attenuated myocardial infarction-induced deterioration of cardiac function, including left ventricular pressure and dP/dt.
- A significant reduction in left ventricular end-diastolic pressure was observed with angiotensin-(1-7) treatment.
- Angiotensin-(1-7) completely preserved aortic endothelial function, unlike in saline-treated infarcted rats.
Conclusions:
- Angiotensin-(1-7) demonstrated a protective effect on cardiac function and coronary perfusion in a heart failure rat model.
- The peptide also preserved aortic endothelial function, suggesting a broad benefit in cardiovascular health.
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