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 angiote nsin converting enzyme (ACE) inhibitors results in peripheral vasodila tation and an increase in cardiac output without an increase in heart rate, which suggests a positive inotropic effect, This cannot be expla ined by changes in angiotensin II and bradykinin concentrations that o ccur. 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 t hat ACE inhibition would increase the myocardial concentration of VIP. 2. Male Sprague-Dawley rats received enalapril (2 mg/kg per day) in t heir drinking water or no therapy for 7 days. On day 7 the rats were a naesthetized and blood was sampled. Hearts and kidneys were then harve sted and snap frozen by immersion in liquid nitrogen. Concentrations o f MP 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 s ignificantly 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 the se agents.