Endorphinergic mechanism in the central cardiovascular and analgesic effects of clonidine.
In urethane-anesthetized male rats, injection of 5 nmol clonidine into the nucleus of the solitary tract (NTS) causes hypotension and bradycardia. These effects are greater in spontaneously hypertensive rats (SHR) and normotensive Sprague-Dawley (SD) rats than in normotensive Wistar-Kyoto (WKY) rats. The effects of clonidine are stereoselectively inhibited by 100 ng intra-NTS naloxone in SHR and SD but not in WKY rats. In SHR, the effects of clonidine are also inhibited by intra-NTS administration of ICI 174864 (a delta-receptor antagonist) but not by beta-funaltrexamine (a mu-receptor antagonist), while in SD rats only the mu- and not the delta-antagonist was effective. Neonatal treatment of SHR with monosodium glutamate (MSG) reduced the beta-endorphin content of the arcuate nucleus and the NTS, reduced the cardiovascular effects of clonidine, and abolished their naloxone sensitivity. MSG treatment of newborn WKY reduced the beta-endorphin content of the arcuate nucleus but not the NTS and did not affect the responses to clonidine. Measurement of pain sensitivity by the formalin test indicated that clonidine was more potent as an analgesic in SHR and SD than in WKY rats, and its effect was inhibited by naloxone (2 mg/kg i.p.) in the former two strains but not in WKY. It is proposed that a naloxone-sensitive component of the cardiovascular effects of clonidine is due to release of a beta-endorphin-like opioid from the NTS, and that this mechanism is present in SHR and SD but not in WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology and Therapeutics, McGill University, Montréal, Que., Canada.
G
G
Kunos
R
R
Mosqueda-Garcia
J A
JA
Mastrianni
F V
FV
Abbott
D000698:Analgesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D004723:Endorphins / Q000502:physiology*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D013045:Species Specificity
D004723:Endorphins; D009270:Naloxone; D003000:Clonidine