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.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects*; D001381:Azepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004285:Dogs; D005260:Female; D005711:Gallopamil / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D002121:Calcium Channel Blockers; D015016:Yohimbine; D005711:Gallopamil; D004246:Dimethylphenylpiperazinium Iodide; C024763:talipexole; D009543:Nifedipine; D007545:Isoproterenol