Antagonism by naltrexone of the hypotension and bradycardia induced by alpha-methyldopa in conscious normotensive rats.
The possible role of the endogenous opioid system in the central hypotensive mechanism of action of alpha-methyldopa was investigated. Conscious normotensive Wistar rats were used in this study and all treatments were given intracisternally. Pretreatment with the opiate receptor antagonist naltrexone resulted in a parallel shift to the right of the dose-response curve for alpha-methyldopa, both for blood pressure and heart rate. In addition, when increasing doses of naltrexone and a constant dose of alpha-methyldopa were used the opiate receptor antagonist inhibited dose-dependently alpha-methyldopa-induced hypotension but not the bradycardia. Administration of naltrexone after the injection of alpha-methyldopa failed to reverse or inhibit alpha-methyldopa-induced hypotension, indicating that the interaction between alpha-methyldopa and the endogenous opioid system occurs at the start of the action of alpha-methyldopa. An antiserum against endorphins also inhibited the fall in blood pressure after alpha-methyldopa. These findings indicate that stimulation of opiate receptors, probably by an endorphin, is involved in the mechanism of action of alpha-methyldopa and that this stimulation seems to occur at the start of the action of alpha-methyldopa.
D000818:Animals; D001919:Bradycardia / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced*; D007106:Immune Sera; D008297:Male; D008750:Methyldopa; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D001615:beta-Endorphin / Q000276:immunology
D007106:Immune Sera; D009270:Naloxone; D008750:Methyldopa; D009271:Naltrexone; D001615:beta-Endorphin