ACUTE HEMODYNAMIC-EFFECTS OF COMBINED INHIBITION OF NEUTRAL ENDOPEPTIDASE AND ANGIOTENSIN-CONVERTING ENZYME IN SPONTANEOUSLY HYPERTENSIVE RATS

Neutral endopeptidase inhibitors (NEPI) potentiate the hypotensive eff ect of converting enzyme inhibitors (CEI) in conscious spontaneously h ypertensive rats (SHR) but the mechanism of this potentiation remains unknown. The present study assesses the hemodynamic effects of a CEI ( enalaprilat 1 mg/kg; n = 9), a NEPI (retrothiorphan 25 mg/kg + 25 mg/k g/h; n = 9) and the combination (CEI + NEPI; n = 9) versus a control g roup (n = 9) in anesthetized spontaneously hypertensive rats. CEI alon e induced a significant hypotensive effect due to a decrease (-35.1%) in total peripheral resistance (TPR), with no significant increase in cardiac output (GO). NEPI alone had a slight hypotensive effect due to a small decrease in CO. CEI + NEPI decreased the mean arterial pressu re to the same extent (-26.7%) as the CEI-induced hypotensive effect, decreased TPR (-44.4%) and induced an increase in CO (+38.2%) with an increase in heart rate. In summary, NEPI combined with CEI induces lar ge decreases in blood pressure and in TPR which do not significantly d iffer from the CEI-induced effects. It also induces increases in heart rate and in cardiac output in anesthetized SHR.