Role of alpha- and beta-adrenergic activation in ventricular fibrillation death of corticoid-pretreated rats.
Death in ventricular fibrillation was induced consistently in desoxycorticosterone acetate-pretreated rats by the beta-adrenergic agonist isoproterenol but not by norepinephrine or epinephrine, both of which possess alpha- as well as beta-adrenergic activity. Aminophylline, which enhances beta-adrenergic activity, and phenoxybenzamine, an alpha-receptor blocking agent, were used to study the roles of alpha- and beta-adrenergic stimulation in the production of ventricular fibrillation. With the addition of aminophylline, both norepinephrine and epinephrine produced death in ventricular fibrillation, and the existing cardiotoxicity of isoproterenol was potentiated. Similarly, in the presence of phenoxylbenzamine, doses of norepinephrine and epinephrine that had been well tolerated became lethal. Internventions that favor beta-adrenergic preponderance, either by enhancing beta-effects or by blocking protective alpha-adrenergic activation, apparently increase the arrhythmogenic propensity of norepinephrine and epinephrine in steroid-pretreated rats. The similarity of some forms of stress to the experimental protocol of chronic steroid treatment followed by acute catecholamine exposure is discussed.
D000316:Adrenergic alpha-Agonists / Q000633:toxicity*; D000318:Adrenergic beta-Agonists / Q000633:toxicity*; D000628:Aminophylline / Q000633:toxicity; D000818:Animals; D002395:Catecholamines / Q000633:toxicity*; D003900:Desoxycorticosterone / Q000633:toxicity*; D004357:Drug Synergism; D004837:Epinephrine / Q000633:toxicity; D007545:Isoproterenol / Q000633:toxicity; D008297:Male; D009638:Norepinephrine / Q000633:toxicity; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D014693:Ventricular Fibrillation / Q000139:chemically induced*
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D010643:Phenoxybenzamine; D000628:Aminophylline; D003900:Desoxycorticosterone; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine