On the relationship between clonidine hypotension and brain beta-endorphin in the spontaneously hypertensive rat: studies with alpha adrenergic and opiate blockers.
The relationship between the centrally mediated hypotensive and bradycardic effects of clonidine to central alpha-2 adrenergic receptor activation, brain beta-endorphin (BE) release and opiate receptor activation was studied in chloralose-anesthetized spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats, using a cerebroventricular perfusion system. Prior treatment of SHRs with i.v. naloxone (2 or 4 mg/kg) or i.c.v. yohimbine (10 or 20 micrograms/kg) reduced the hypotension and bradycardia induced by i.c.v. clonidine, but in Wistar-Kyoto rats naloxone had no similar blocking effects. Prazosin (20 micrograms/kg i.c.v.) reduced the clonidine bradycardia but not the hypotension in SHRs. Hypotension in the SHRs due to i.c.v. alpha-methylnorepinephrine (20 micrograms/kg) was reduced by both naloxone and yohimbine whereas alpha-methylnorepinephrine bradycardia was reduced by yohimbine but not by naloxone. Prior hypothalamic lesions in the SHRs reduced clonidine hypotension, but not bradycardia, and interfered with naloxone blockade of the residual clonidine hypotensive effect. Clonidine lowered immunoreactive BE levels in SHR hypothalamus, medulla and pituitary but did not change BE levels in the i.c.v. perfusate. The findings support the idea that in the SHRs, clonidine hypotension results from alpha-2 adrenergic stimulation of brain, causing BE release and central opiate receptor activation, and they suggest that the hypothalamus is involved in these interactions. Also, clonidine hypotension and bradycardia appear to involve different mechanisms in brain.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology*; D004723:Endorphins / Q000134:cerebrospinal fluid / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D007031:Hypothalamus / Q000502:physiology; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology; D001615:beta-Endorphin
D004723:Endorphins; D011942:Receptors, Adrenergic, alpha; D011957:Receptors, Opioid; D015016:Yohimbine; D009270:Naloxone; D001615:beta-Endorphin; D003000:Clonidine; D011224:Prazosin