DIFFERENTIAL-EFFECTS OF NIFEDIPINE, NICORANDIL AND NITROGLYCERIN ON THE PRESSOR-RESPONSES ELICITED BY SELECTIVE ALPHA-1 AND ALPHA-2 ADRENOCEPTOR AGONISTS IN CONSCIOUS DOGS

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Abstract
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 .mu.g/kg i.v.), a selective alpha-1 adrenoceptor agonist, and B-HT 933(20 .mu.g/kg i.v.) a selective alpha-2 adrenoceptor agonist, were administered before and in the presence of infusions of nifedepine (0.25-2.0 .mu.g/kg/min), nicorandil (4.0-32.0 .mu.g/kg/min) or nitroglycerin (1.0-8.0 .mu./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 of 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 .mu./kg i.v.) and B-HT 933 (10, 20 and 40 .mu.g/kg i.v.) were administered before and after i.v. infusions of nifedipine (1.0 .mu.g/kg/min) or nicorandil (16.0 .mu.g/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 presure by nicorandil was partially overcome at higher doses (40 .mu.g/kg) of B-HT 933. Thus, in conscious dogs, alpha-1- and alpha-2-mediated pressor responses were differently influenced by three mechanistically distinct vasodilators, nifedipine, nicorandil and nitroglycerin, despite similar reductions in mean arterial pressure produced by all three agents. Whereas nifedipine significantly attenuated both alpha-1 and alpha-2-mediated pressor responses, nicorandil selectively inhibited only alpha-2-mediated increases in arterial pressure in conscious dogs.