Abstract

The effects of the Ca entry blockers nifedipine and verapamil on the contractions induced by phenylephrine (PHE) in rat isolated aorta and mesenteric vascular bed (MVB) were evaluated. The main goal was to elucidate whether differences among blood vessels in their receptor reserves are involved in the different degrees to which Ca antagonists inhibit alpha adrenergic vasoconstriction. In the two tissues the responses to the full agonist PHE were antagonized by prazosin with an at least 1000-fold greater potency than by yohimbine. The -log KB values for both antagonists in the aorta (11.07 and 7.40, respectively) were significantly higher than those in the MVB (9.77 and 6.43, respectively), thus suggesting receptor heterogeneity between the two tissues. Both nifedipine and verapamil were more effective in reducing the responses in the MVB (maximal inhibition, 54.3 +/- 1.9 and 55.0 +/- 3.5%) than in the aorta (25.2 +/- 5.8 and 30.4 +/- 0.7%). Studies with phenoxybenzamine (PB) indicated that in the latter case the responses were associated with an effective receptor reserve of about 40%, whereas in the MVB no spare receptors for the full agonist were available. Pretreatment of the MVB with PB showed no effect on the inhibitory action of verapamil. Conversely, removal of the spare receptors in the aorta (10(-10) M PB) rendered the responses more susceptible to inhibition by verapamil. Pretreatment of the aortic strips with 10(-9) M PB, however, failed to enhance further the effectiveness of verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)