Possible involvement of an endogenous opioid in the antihypertensive effect of clonidine in patients with essential hypertension.
The effect of naloxone on the hypotensive and bradycardiac action of clonidine was studied in 27 hospitalized patients with uncomplicated mild-to-moderate essential hypertension. In a double-blind, crossover study, clonidine, 0.3 mg/day orally for 3 days, significantly reduced systolic and diastolic blood pressure and heart rate, whereas placebo was ineffective. Naloxone, 0.4 mg given intravenously on the third day of clonidine treatment, caused a rapid increase in blood pressure and heart rate in 14 patients (reacting group), but was ineffective in the remaining 13 patients (nonreacting group). Naloxone given during the placebo period was ineffective in all patients. Both the clonidine-induced hypotension and the rebound increase in blood pressure after cessation of clonidine were significantly greater in the reacting than in the nonreacting group. These observations suggest that release of an endogenous opioid contributes to the antihypertensive action of clonidine; this mechanism may be also involved in the discontinuation syndrome after cessation of clonidine.
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000627:therapeutic use*; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008875:Middle Aged; D009270:Naloxone / Q000494:pharmacology*; D010919:Placebos; D011957:Receptors, Opioid / Q000187:drug effects
D010919:Placebos; D011957:Receptors, Opioid; D009270:Naloxone; D003000:Clonidine