Opioid-mediated cardiovascular effects of clonidine in spontaneously hypertensive rats: elimination by neonatal treatment with monosodium glutamate.
The interaction between clonidine and opiate receptor antagonists on arterial blood pressure (BP) and heart rate were examined in normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). In conscious SHR, the hypotension and bradycardia caused by clonidine, 5 micrograms/kg iv, were significantly attenuated by naltrexone, 2 mg/kg ip. In urethane-anesthetized SHR, the reduction in mean BP and heart rate in response to 5 nmol clonidine microinjected into the nucleus of the solitary tract (NTS), were similarly inhibited after intra-NTS microinjection of 100 ng DL-naloxone but not after the same dose of D-naloxone. Neonatal treatment of SHR by monosodium glutamate (MSG) markedly reduced the beta-endorphin (BE) but not the leucin-enkephalin content of the arcuate nucleus and the NTS. MSG treatment did not affect the basal BP of these animals, but significantly reduced the hypotensive effect of clonidine and eliminated its susceptibility to opiate antagonists in both conscious and anesthetized SHR. In conscious and anesthetized WKY, the cardiovascular effects of clonidine were smaller than in SHR and were unaffected by naloxone or naltrexone. Neonatal treatment of WKY with MSG reduced the BE content of the arcuate nucleus but not of the NTS. MSG treatment of WKY did not influence either basal BP or the cardiovascular effects of clonidine, and the latter remained unaffected by opiate antagonists. These findings support the hypothesis that in SHR, but not in WKY, the centrally mediated cardiovascular effects of clonidine are partially mediated by the release of a BE-like opioid. They also strongly suggest that the site of both the release and the action of this opioid is in the NTS.
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D004723:Endorphins / Q000378:metabolism / Q000502:physiology*; D004743:Enkephalin, Leucine / Q000378:metabolism; D005971:Glutamates / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000503:physiopathology*; D008526:Medulla Oblongata / Q000187:drug effects / Q000503:physiopathology; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012970:Sodium Glutamate / Q000494:pharmacology*; D001615:beta-Endorphin
D004723:Endorphins; D005971:Glutamates; D009270:Naloxone; D004743:Enkephalin, Leucine; D009271:Naltrexone; D001615:beta-Endorphin; D003000:Clonidine; D012970:Sodium Glutamate