Inhibition of vasoconstriction to cirazoline by calcium-entry blockade after phenoxybenzamine in rat perfused hindquarters

Abstract

The effects of phenoxybenzamine and benextramine were assessed with respect to the vasoconstriction to cirazoline in rat perfused hindquarters. Experiments were performed with and without restriction of inward calcium flux by addition of nifedipine (10(-9)-10(-6) M) to the standard physiological solution (PS), or by omission of calcium chloride from the PS. Addition of nifedipine or omission of Ca2+ did not affect the maximal response or potency of the selective but partial alpha 1-adrenoceptor agonist, cirazoline in rat perfused hindquarters. Upon pretreatment with phenoxybenzamine (0.03-30 micrograms/kg, i.v. at -1 h) or benextramine (1 mg/kg, i.v. at -2 h) both the slope and the maximal response to cirazoline were depressed. After phenoxybenzamine but not after benextramine the maximal response to cirazoline was depressed further upon addition of nifedipine or omission of Ca2+ from the PS. It is concluded that phenoxybenzamine selectively inhibits that part of the alpha 1-adrenoceptor mediated vasoconstriction that is independent of extracellular calcium, thereby unmasking a calcium-entry sensitive mechanism of vasoconstriction to cirazoline.