title: Reversal by naloxone of the antihypertensive action of clonidine: involvement of the sympathetic nervous system.
abstract: The effects of clonidine, naloxone, and their combination on arterial blood pressure (BP), heart rate (HR), and hemodynamic and biochemical parameters were examined in 29 patients with essential hypertension. Treatment for 3 days with 0.3 mg/day clonidine reduced BP and HR, and these effects were quickly reversed by a single injection of 0.4 mg iv naloxone in 17 of the patients (responders), but not in the remaining 12 (nonresponders). Responders had higher control values for cardiac output, stroke index, plasma renin activity (PRA), and plasma epinephrine levels than did nonresponders. Basal BP was similar in the two groups, but clonidine decreased BP, PRA, and plasma epinephrine more in responders than in nonresponders. Naloxone given during placebo treatment had no significant effects. During clonidine treatment naloxone increased BP, HR, total peripheral resistance, PRA, and plasma epinephrine and norepinephrine, and decreased stroke volume in responders, whereas in nonresponders its only effect was a small increase in HR. It is concluded that in a subset of hyperadrenergic, hypertensive patients the antihypertensive effect of clonidine involves a naloxone-reversible inhibition of central sympathetic outflow, probably mediated by the release of an endogenous opioid.
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D004837:Epinephrine / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008875:Middle Aged; D009270:Naloxone / Q000008:administration & dosage*; D009638:Norepinephrine / Q000097:blood; D012083:Renin / Q000097:blood; D013318:Stroke Volume / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000503:physiopathology*
chemical_list: D006852:Hydrochlorothiazide; D009270:Naloxone; D012083:Renin; D003000:Clonidine; D009638:Norepinephrine; D004837:Epinephrine