Increases in the myocardial concentration of vasoactive intestinal peptide may explain the positive inotropic effect of angiotensin converting enzyme inhibitors.
1. In patients with congestive cardiac failure, treatment with angiotensin converting enzyme (ACE) inhibitors results in peripheral vasodilatation and an increase in cardiac output without an increase in heart rate, which suggests a positive inotropic effect. This cannot be explained by changes in angiotensin II and bradykinin concentrations that occur. ACE has been suggested to also metabolise vasoactive intestinal peptide (VIP), which is a positive inotrope. As VIP is synthesized by the heart and acts locally to increase cardiac output, we postulated that ACE inhibition would increase the myocardial concentration of VIP. 2. Male Sprague-Dawley rats received enalapril (2 mg/kg per day) in their drinking water or no therapy for 7 days. On day 7 the rats were anaesthetized and blood was sampled. Hearts and kidneys were then harvested and snap frozen by immersion in liquid nitrogen. Concentrations of VIP in plasma and tissue extracts were measured by radioimmunoassay. 3. Plasma and renal concentrations of VIP did not change in enalapril-treated rats. However, the myocardial concentration of VIP increased significantly in rats receiving enalapril compared with control animals (P < 0.0005). 4. We conclude that treatment with ACE inhibitors results in increased myocardial VIP concentrations and suggest that this may contribute to the improvement in cardiac function that occurs with these agents.
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Hypertension Service, Liverpool Hospital, Sydney, New South Wales, Australia.
Duggan
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D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004656:Enalapril / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014660:Vasoactive Intestinal Peptide / Q000097:blood / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D002316:Cardiotonic Agents; D014660:Vasoactive Intestinal Peptide; D004656:Enalapril