The present study was performed to gain more information on the nature of the opioid peptide(s) involved in the mechanism of action of α-methyldopa. Conscious, normotensive Wistar rats were used and all treatments were given intracisternally. For blood pressure and heart rate, pretreatment with a midportion β-endorphin antiserum resulted in a parallel shift to the right of the dose-response curve for α-methyldopa. In addition, when rats were pretreated with various dilutions of this antiserum and treated with a constant dose of α-methyldopa, the antiserum dose-dependently inhibited α-methyldopa-induced hypotension and bradycardia. Using antisera specifically recognizing the C-terminus of β-, γ- and α-endorphin, respectively, revealed that only the β-endorphin antiserum inhibited the decrease in blood pressure seen after administration of α-methyldopa. An antiserum against [Met5]enkephalin did not influence the cardiovascular responses following α-methyldopa. On the other hand, a dynorphin(1–13) antiserum also inhibited in a dose-dependent manner the hypotension induced by α-methyldopa. When administered 3 h after the injection of α-methyldopa, the β-endorphin and dynorphin(1–13) antisera failed to reverse the hypotension induced by α-methyldopa. The results favor a role for β-endorphin(1-31) and dynorphin(l-13) in the hypotension centrally mediated by α-methyldopa.

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