Possible involvement of brain opioid peptides in clonidine-induced hypotension in spontaneously hypertensive rats.
The effect of intracisternal pretreatment with opiate antagonists or antisera against various opioid peptides on the hypotension and bradycardia induced by cumulative intracisternal administration of clonidine (0.02-2.5 microgram) was studied in conscious Wistar-Kyoto rats and in spontaneously hypertensive rats. No effect of any pretreatment on basal values of blood pressure and heart rate was detected in either of these strains. In spontaneously hypertensive rats intracisternal pretreatment with naltrexone resulted in a dose-dependent inhibition of clonidine-induced hypotension and bradycardia. DL-naloxone also antagonized the hypotension but not influence the hypotensive and bradycardic response to clonidine. In Wistar-Kyoto rats naltrexone and the beta-endorphin antiserum B4 failed to affect the cardiovascular effects of clonidine. B4 and an antiserum against dynorphin(1-13) inhibited clonidine-induced hypotension in spontaneously hypertensive rats, whereas a [Met5]enkephalin antiserum had no effect. Use of antisera specifically recognizing the C-terminus of beta-, alpha-, and gamma-endorphin, respectively, revealed that only the beta-endorphin antiserum inhibited the fall in blood pressure in spontaneously hypertensive rats after cumulative administration of clonidine. None of the antisera used affected clonidine-induced bradycardia. These results indicate that activation of stereospecific opiate receptors in spontaneously hypertensive, but not in Wistar-Kyoto rats, plays a role in the central hypotensive effect of clonidine. beta-Endorphin(1-31) and dynorphin(1-13) might be the endogenous ligands for these receptors.
van Giersbergen
P L
PL
Rudolf Magnus Institute, Medical Faculty, State University of Utrecht, The Netherlands.
Tierney
S A
SA
Wiegant
V M
VM
de Jong
W
W
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology*; D004723:Endorphins / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009271:Naltrexone / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D011957:Receptors, Opioid / Q000187:drug effects; D012970:Sodium Glutamate / Q000494:pharmacology
D004723:Endorphins; D011957:Receptors, Opioid; D009271:Naltrexone; D003000:Clonidine; D012970:Sodium Glutamate