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Differential effects of nifedipine, nicorandil and nitroglycerin on the pressor responses elicited by selective alpha-1 and alpha-adrenoceptor agonists in conscious dogs

JC Wynsen, GJ Gross, HL Brooks and DC Warltier

The influence of vasodilators with varying mechanisms of action on pressor responses mediated by alpha-1 and alpha-2 adrenoceptors was investigated in chronically instrumented, conscious dogs. After ganglionic, cholinergic and beta adrenergic blockade, equipressor doses of phenylephrine (0.6 microgram/kg i.v.), a selective alpha-1 adrenoceptor agonist, and B-HT 933 (20 micrograms/kg i.v.) a selective alpha-2 adrenoceptor agonist, were administered before and in the presence of infusions of nifedipine (0.25-2.0 micrograms/kg/min), nicorandil (4.0-32.0 micrograms/kg/min) or nitroglycerin (1.0-8.0 micrograms/kg/min). Nifedipine produced a dose-related attenuation of the increase in mean arterial pressure after bolus administration of phenylephrine (from 26 +/- 1 to 7 +/- 1 mm Hg) and B-HT 933 (from 29 +/- 2 to 5 +/- 1 mm Hg). Nicorandil did not affect phenylephrine-mediated pressor responses but significantly attenuated those to B-HT 933 (28 +/- 2 to 10 +/- 1 mm Hg). In contrast, nitroglycerin had no effect on either phenylephrine or B-HT 933-mediated responses. In additional experiments after autonomic nervous system blockade, multiple doses of phenylephrine (0.6, 1.25 and 2.5 micrograms/kg i.v.) and B-HT 933 (10, 20 and 40 micrograms/kg i.v.) were administered before and after i.v. infusions of nifedipine (1.0 microgram/kg/min) or nicorandil (16.0 micrograms/kg/min). Nifedipine significantly decreased the pressor responses to all doses of phenylephrine and B-HT 933. In contrast, the attenuation from control of alpha-2-mediated increases in arterial pressure by nicorandil was partially overcome at higher doses (40 micrograms/kg) of B-HT 933.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 241, Issue 3, pp. 846-854, 06/01/1987
Copyright © 1987 by American Society for Pharmacology and Experimental Therapeutics






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Copyright © 1987 by the American Society for Pharmacology and Experimental Therapeutics.