ENDOGENOUS OPIOID PEPTIDE INHIBITION OF THE CENTRAL ACTIONS OF ANGIOTENSIN

Abstract

Effects of endogenous opioid peptides (leucine5-enkephalin, methionine5-enkephalin and .beta.-endorphin) and morphine on isoleucine5-angiotensin II (AII) stimulated increase in plasma vasopressin concentration, blood pressure and drinking behavior were characterized in conscious rats. Plama vasopressin concentration, drinking frequency and latency were measured 90s after intracerebroventricular (i.v.t.) AII in animals pretreated with enkephalins, .beta.-endorphin or morphine, i.v.t. Vasopressin was measured by radiommunoassay. A consistent dose-related, naloxone-sensitive inhibition of the AII-stimulated increase in plasma vasopressin concentration and drinking behavior (frequency) occurred after enkephalins, .beta.-endorphin or morphine. .beta.-Endorphin and morphine were longer acting and more potent than enkephalins. In other experiments, AII (i.v.t.) pressor activity, drinking volume and latency were measured at hourly intervals after opiates, i.v.t. The AII-stimulated increase in mean blood pressure and drinking volume were inhibited by endogenous opioid peptides and morphine, i.v.t. Naloxone prevented opiate inhibition of the AII pressor response. Endogenously synthesized opiates may modulate AII activity as naloxone potentiated the pressor response and decreased water consumption after AII, i.v.t. Continuous i.v. infusion of leucine-enkephalin did not affect AII drinking or pressor activity, indicating a CNS site of inhibition. Opiate inhibition of the central actions of AII appeared independent of sedation; head shakes or wet dog shakes occurred at effective doses of enkephalins. Naloxone did not affect basal blood pressure or plasma vasopressin concentration. Endogenous opioid peptides may modulate the central actions of angiotensin II affecting blood pressure and hydration.