Calcium Entry Blockade and Alpha-Adrenergic Responsiveness In Vivo

Abstract

In an initial series of studies in pithed normotensive rats, nitrendipine (3, 10, 30 micrograms/kg/min X 15 min) preferentially antagonized the pressor responses to BHT 920, a selective alpha 2-adrenergic agonist, while hardly interfering with responses to methoxamine, a selective alpha 1-agonist. The preferential alpha 2-antagonism by nitrendipine (0.01-0.3 mg/kg i.v.) was also shown by its greater antagonism of pressor responses to norepinephrine in propranolol (1 mg/kg)-prazosin (0.3 mg/kg i.v.)-pretreated pithed rats (alpha 1-receptors blocked, alpha 2 exposed) than in propranolol-yohimbine (0.3 mg/kg)-pretreated preparations (alpha 2 blocked, alpha 1 exposed). However, the effect of nitrendipine on vascular alpha 2-adrenergic responsiveness was found to be not specific for calcium entry blockers (CaEB) since vasodilators without calcium entry blocking properties [sodium nitroprusside (3-30 mg/kg/min X 15 min) and hydralazine (0.03-3.0 mg/kg/min X 15)], gave the same pattern of interference with pressor responses to methoxamine and BHT 920 in exactly the same model. Both vasodilators depressed the pressor dose-response curves to BHT 920, while sparing those to methoxamine. Thus, calcium entry blockade preferentially antagonized alpha 2-mediated vasoconstriction, but this effect was common to other non-CaEB vasodilators. The reason for the relative sparing by CaEB of pressor responses to alpha 1-adrenergic stimulation was sought in a second series of studies of dose-response curves to methoxamine following partial alpha-adrenoceptor inactivation by phenoxybenzamine (0.3 mg/kg i.v.). In these conditions, nitrendipine (30 micrograms/kg/min), sodium nitroprusside (30 micrograms/kg/min), and hydralazine (3 mg/kg/min) all strongly depressed the pressor responses to methoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)