Possible involvement of beta endorphin(1-31) and dynorphin(1-13) in the central hypotensive mechanism of action of alpha methyldopa.
The present study was performed to gain more information on the nature of the opioid peptide(s) involved in the mechanism of action of alpha-methyldopa. Conscious, normotensive Wistar rats were used and all treatments were given intracisternally. For blood pressure and heart rate, pretreatment with a midportion beta-endorphin antiserum resulted in a parallel shift to the right of the dose-response curve for alpha-methyldopa. In addition, when rats were pretreated with various dilutions of this antiserum and treated with a constant dose of alpha-methyldopa, the antiserum dose-dependently inhibited alpha-methyldopa-induced hypotension and bradycardia. Using antisera specifically recognizing the C-terminus of beta-, gamma- and alpha-endorphin, respectively, revealed that only the beta-endorphin antiserum inhibited the decrease in blood pressure seen after administration of alpha-methyldopa. An antiserum against [Met5]enkephalin did not influence the cardiovascular responses following alpha-methyldopa. On the other hand, a dynorphin(1-13) antiserum also inhibited in a dose-dependent manner the hypotension induced by alpha-methyldopa. When administered 3 h after the injection of alpha-methyldopa, the beta-endorphin and dynorphin(1-13) antisera failed to reverse the hypotension induced by alpha-methyldopa. The results favor a role for beta-endorphin(1-31) and dynorphin(1-13) in the hypotension centrally mediated by alpha-methyldopa.
van Giersbergen
P L
PL
Rudolf Magnus Institute for Pharmacology, Medical Faculty, State University of Utrecht, The Netherlands.
Wiegant
V M
VM
de Jong
W
W
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002946:Cisterna Magna; D004399:Dynorphins / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007267:Injections; D008297:Male; D008750:Methyldopa / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D001615:beta-Endorphin / Q000494:pharmacology*
D000700:Analgesics; D010446:Peptide Fragments; D008750:Methyldopa; D001615:beta-Endorphin; C026843:dynorphin (1-13); D004399:Dynorphins