Equal potency of nifedipine to inhibit α1-(dobutamine and BDF 6143) and α2-adrenoceptor (B-HT 920) induced pressor responses in pithed rats; lack of effect of phenoxybenzamine

Abstract

Intravenous (i.v.) dobutamine and BDF 6143 were partial agonists in increasing diastolic pressure in β-adrenoceptor-blocked pithed rats. The log dose-pressor effect curves were not influenced by yohimbine (1 mg/kg i.v., −15 min) but were markedly shifted to the right by prazosin (0.1 mg/kg i.v., −15 min) indicating the exclusive involvement of α 1-adrenoceptors. Nifedipine (0.1–1 mg/kg i.a., −15 min) non-competitively inhibited the pressor effects of dobutamine and BDF 6143 as well as of the α 2-adrenoceptor agent B-HT 920 with equal potency. The −log ED 50 values calculated for nifedipine amounted to 6.25 ± 0.12, 6.16 ± 0.14 and 6.20 ± 0.10, respectively. Phenoxybenzamine (3 or 10 μg/kg i.v., −60 min) did not affect the effectiveness of nifedipine (0.1 mg/kg) to inhibit the pressor effects of dobutamine and BDF 6143. Following treatment with Bay k 8644 (1 mg/kg i.a., −15 min), the log dose-pressor effect curves for dobutamine and BDF 6143 were shifted to the left and the maximum responses were elevated. Our findings suggest that the α 1-adrenoceptor-induced pressor effects of dobutamine and BDF 6143 rely heavily on the influx of Ca 2+, and are indistinguishable in this respect from the effects initiated by α 2-adrenoceptor stimulation. The data further support the view that the sensitivity of α-adrenoceptor-mediated pressor effects to inhibition by Ca 2+ entry blockers depends on the extent to which Ca 2+ influx contributes to the overall response and is not determined by the intrinsic activity or by the receptor reserve of the α-adrenoceptor agonist.