Effects of nifedipine on the hypotensive actions of alpha 2-agonists in conscious spontaneously hypertensive rats.

Abstract

The present study was designed to examine the effects of the calcium entry blocker, nifedipine, on the acute depressor responses to alpha 2-adrenoceptor agonists. Conscious spontaneously hypertensive rats (SHR) were given nifedipine intravenously (25 micrograms/kg) or vehicle (polyethylene glycol). Subsequent intravenous administration of guanabenz (10, 25, or 50 micrograms/kg) or clonidine (5 micrograms/kg) caused biphasic changes in mean arterial pressure (MAP) in vehicle-treated SHR, an initial pressor response, which was followed by a sustained fall in MAP. In nifedipine-treated rats, the pressor actions of guanabenz and clonidine were virtually abolished, while the onset of the depressor responses were significantly accelerated. The maximal depressor responses to guanabenz and clonidine were similar in vehicle- and nifedipine-pretreated SHR. Central administration of nifedipine (5, 10, or 20 micrograms/kg) in the lateral cerebroventricle significantly attenuated the depressor responses to guanabenz in a dose-dependent manner as compared to vehicle-treated rats. Oral pretreatment with nifedipine (2.5 mg/kg) also significantly blunted the hypotensive actions of guanabenz in the conscious SHR. These data indicate that central and oral administration of nifedipine antagonized the centrally mediated hypotensive actions of guanabenz. Intravenous bolus administration of nifedipine failed to attenuate the maximal depressor responses to guanabenz, suggesting that insufficient nifedipine accumulated centrally to affect central alpha 2-adrenoceptor function.