A comparison of the effects of acute versus chronic administration of phenoxybenzamine on pressor responses elicited by the selective α1-adrenoceptor agonist cirazoline in the pithed rat preparation
The effects of nifedipine on the pressor responses to cirazoline were examined in the pithed rat preparation that had received either acute or chronic phenoxybenzamine treatment. Phenoxybenzamine was administered, i.v., to conscious rats, either acutely at 0.01, 0.03, and 0.1 mg/kg, 60 min prior to the commencement of the experiments or chronically at 0.1, 0.3, and 1.0 mg/kg, once daily for 7 days. Nifedipine was administered i.a. (1.0 mg/kg) after the animals had been pithed. The acute or chronic administration of phenoxybenzamine alone displaced the dose-response curve to cirazoline to the right in a dose-dependent manner, while reducing the slope function and maximum response to the agonist. The combined effects of acute phenoxybenzamine and nifedipine produced an additive inhibitory effect on the pressor response elicited by cirazoline, which was most apparent following the removal of receptor reserve by acute phenoxybenzamine. The inhibitory effects of nifedipine and chronically administered phenoxybenzamine were additive at the lower administered doses of the alkylating agent but, in contrast with the effects of acute phenoxybenzamine, the enhanced inhibitory effects of nifedipine were reduced following the removal of receptor reserve. These results indicate that the chronic administration of phenoxybenzamine reduces the additive inhibitory effects of nifedipine and phenoxybenzamine that were observed following the acute administration of phenoxybenzamine.