• The Korean Journal of Pharmacology
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• v.23 no.2
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• pp.123-131
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• 1987

The possible inolvement of central opiate system in the control of cardiovascular function and in the antihypertensive action of clonidine has been examined in unanesthetized rats with shamoperated or 2-kidney, 1-clip (2K1C) renal hypertension. In both groups of rats, intraventricular clonidine $(3-30\;{\mu}g/kg)$ produced hypotension and bradycardia. Hypotensive action of clonidine was more potent in the hypertensive rats than in the normotensive sham-operated rats. Yohimbine $(30\;{\mu}g/kg,\;i.v.t.)$ inhibited the hypotension and bradycardia produced by clonidine. Naloxone ($50\;{\mu}g/kg$, i.v.t.) inhibited the action of clonidine in 2K1C hypertensive rats but not influenced in the sham-operated rats. Intraventricular morphine $(10-100\;{\mu}g/kg)$ also reduced rats. Intraventricular morphine $(10-100\;{\mu}g/kg)$ also reduced blood pressure and heart rate in both groups of rats. But these effects were not affected by yohimbine, but antagonized by naloxone ($50\;{\mu}g/kg$, i.v.t.). Chronic treatment of 2K1C rats with clonidine ($3{\times}20\;{\mu}g/kg$, p.o.,) for 14 days from 1 day after 2K1C operation) suppressed the development of hypertension and maintained the blood pressure in normal level and this errect of clonidine was abolished by naloxone (2 mg/kg, i. p.). In the 2K1C hypertensive rats, immunoreactive ${\beta}-endorphin$ content was significantly decreased, but maximum binding (Bmax) of $(^3H)-naloxone$ was significantly increased in brain of 2K1C hypertensive rats. However, Kd value was not changed. These results suggest that the opioidergic component might be involved in the antihypertensive action of clonidine only in hypertensive and that central opiate system might play important roles in pathophysiology of development and maintenance of hypertension.