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Supplementation of the antihypertensive action of the peripheral vasodilator sodium nitroprusside (SNP) with clonidine, a centrally-acting agent, was studied in ten dogs anesthetized with isoflurane to evaluate the efficacy of clonidine for reducing the amount of SNP required during induced hypotension. The dose of SNP required to lower mean arterial blood pressure (MAP) by 40% was determined prior to the administration of intravenous clonidine (control), and after incremental doses of 1, 4, and 15 figlkg. After each dose of clonidine, hypotension was induced with SNP and maintained for 30 min, followed by a 30-min recovery period. Plasma levels of norepinephrine (NE) and epinephrine (EPI) were determined before hypotension, at 5 min and 30 min during hypotension, and at 5 min and 30 min during recovery. During the control period (no clonidine), SNP-induced hypotension resulted in increases in plasma cate-cholamine levels, with larger increases in EPI (from 70 ± 26 to 851 ± 140 pg/ml, at 30 min) than NE (from 171 ± 26 to 334 ± 58 pg/ml, at 30 min). There was no significant difference between the control MAP and the MAP after each incremental dose of clonidine. In these anesthetized dogs with low sympathetic tone there was no significant decrease in EPI levels after administration of up to 20 μg/kg of clonidine. Increasing doses of clonidine correlated inversely with depression in catecholamine output during induced hypotension and the dose of SNP required to produce this hypotension. The cumulative dose of 20 μg/kg of clonidine prevented hypotension-induced increases in circulating cate-cholamines and decreased the dose requirement of SNP by 81%, suggesting that as much as 80% of the SNP dose is in response to baroreceptor-mediated increase in sympathetic activity. The attenuation of sympathetic discharge by clonidine during anesthesia, without change in resting MAP, makes it a potentially useful ancillary agent for reducing the amount of SNP used to produce controlled hypotension.