Invariable susceptibility to blockade by nifedipine of vasoconstriction to various alpha 2-adrenoceptor agonists in pithed rats.

The sensitivity of the increase in diastolic pressure brought about by the selective agonists of alpha 2-adrenoceptors, B-HT 920, B-HT 933, xylazine, UK-14,304, M-7, TL-99 and DP-6, 7-ADTN in pithed normotensive rats to blockade by the calcium entry inhibitor nifedipine has been investigated. To exclude any participation of vascular alpha 1- and beta 2-adrenoceptors, as well as cardiac beta 1-adrenoceptors, in the pressor responses, the study was made after treatment of the pithed rats with prazosin (0.1 mg kg-1) and (-)-propranol (1 mg kg-1). Without exception, the preferential agonists of alpha 2-adrenoceptors elicited vasoconstrictor responses which were susceptible to inhibition by nifedipine (0.03-1 mg kg-1) in a dose-dependent manner regardless of the differences in intrinsic activity of the compounds. The pressor activity was almost completely abolished after 1 mg kg-1 of nifedipine. The results show that vasoconstriction induced in pithed rats by various selective stimulating agents of postjunctional vascular alpha 2-adrenoceptors is invariably and equally sensitive to attenuation by nifedipine. This susceptibility of alpha 2-adrenoceptor-mediated vasoconstriction to impairment by blockade of calcium entry is not dependent on the nature, the potency or the efficacy of the agonist.