Evaluation of calcium entry blockers and alpha 2-adrenergic antagonists on B-HT 920-induced pressor responses in the autonomically blocked dog.

Several calcium entry blockers and alpha 2-adrenergic receptor antagonists were evaluated for inhibition of pressor responses induced by the selective alpha 2 agonist B-HT 920 in pentobarbital-anesthetized dogs pretreated with prazosin (0.5 mg/kg, i.v.), propranolol (0.5 mg/kg, i.v.), and hexamethonium (10 mg/kg i.v.). In this preparation, autonomic blockade (alpha 1, beta, and ganglionic block) persists for approximately 4 hr. The B-HT 920 administered intravenously causes dose-related increases in mean arterial blood pressure (ED50 = 4.90 micrograms/kg, i.v., dose causing a 50 mm Hg rise in mean arterial blood pressure). Maximum increases in mean arterial pressure approximate 80 mm Hg at 100 micrograms/kg, i.v. Repeated bolus administration of B-HT 920 over a 4-hr period shows no significant reduction in the pressor response, suggesting good stability of this experimental model and no rapidly developing tolerance. Calcium entry blockers (nifedipine, D-600, and diltiazem) and alpha 2-adrenergic receptor antagonists (yohimbine and idazoxan) inhibit the B-HT 920-induced pressor response in a dose-related manner. The ED50 values (dose of antagonist that causes a 50% inhibition of B-HT 920-induced pressor response) were calculated. Idazoxan and yohimbine have ED50 values (mg/kg, i.v.) of 0.086 and 0.063, respectively, whereas D-600, nifedipine, and diltiazem have values of 0.074, 0.111, and 0.542, respectively. The data show that calcium entry blockers and alpha 2-adrenergic blockers are potent inhibitors of B-HT 920 pressor responses in the autonomically blocked dog. This experimental model is appropriate for the evaluation of calcium entry blockers and/or alpha 2-adrenergic antagonists in vivo.