Angiotensin-converting enzyme inhibition with enalapril increases the cardiac concentration of vasoactive intestinal peptide.
In patients with congestive cardiac failure, treatment with 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 the changes in angiotensin II and bradykinin concentrations that occur. It has been suggested that ACE also metabolizes VIP, which is a positive inotrope. As VIP is synthetized by the heart and acts locally to increase cardiac output, we postulated that ACE inhibition would increase the myocardial concentration of VIP. Male Sprague-Dawley rats received enalapril (2 mg/kg/day) in the drinking water or no therapy for seven days. On day seven they were anaesthetized and blood sampled. The 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. Plasma and renal concentrations of VIP did not change in the enalapril-treated rats. However, the myocardial concentration of VIP increased significantly in the rats receiving enalapril compared with control animals (p < 0.0005). 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.
Duggan
K A
KA
University of Medicine, Prince Henry Hospital, Sydney, Australia.
Ye
V Z
VZ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D004656:Enalapril / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014660:Vasoactive Intestinal Peptide / Q000097:blood / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D014660:Vasoactive Intestinal Peptide; D004656:Enalapril