TY - JOUR T1 - Antagonism by naltrexone of the hypotension and bradycardia induced by alpha-methyldopa in conscious normotensive rats. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 341 LP - 347 VL - 244 IS - 1 AU - P L van Giersbergen AU - W de Jong Y1 - 1988/01/01 UR - http://jpet.aspetjournals.org/content/244/1/341.abstract N2 - 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. ER -