Involvement of G proteins and Rho kinase in α1-adrenoceptor mediated contractions of the rat portal vein

Abstract

Contractions of the rat portal vein in response to the α1-adrenoceptor agonist phenylephrine consist of phasic contractions at low concentrations, with tonic contractions superimposed at higher concentrations. The α1D-adrenoceptor antagonist BMY7378 (7.0, –log M) did not affect phasic or tonic contractions to phenylephrine. The relatively nonselective α1-adrenoceptor antagonist prazosin (7.5) shifted equally the potencies of phenylephrine at producing phasic and tonic contractions, with pKB values of 8.85 and 8.83 (–log M), respectively. The α1A-adrenoceptor antagonist RS100329 (8.5) produced a significantly greater shift in phenylephrine potency for phasic (pKB of 10.51) than tonic contractions (pKB of 9.78). Prazosin was less effective than RS100329 at reducing the effects of phenylephrine on frequency of phasic contractions. The Rho kinase inhibitor fasudil (5.0) did not affect phasic contractions to phenylephrine, but significantly reduced tonic contractions. It is concluded that there is no evidence for involvement of α1D-adrenoceptors in responses of the rat portal vein to phenylephrine, but phasic responses involve predominantly α1A-adrenoceptors. Tonic responses may involve predominantly α1B-adrenoceptors and are at least partly mediated by mechanisms involving Rho kinase sensitive to fasudil.