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

Contractions of the rat portal vein in response to the α-adrenoceptor agonist phenylephrine consist of phasic contractions at low concentrations, with tonic contractions superimposed at higher concentrations. The α-adrenoceptor antagonist BMY7378 (7.0, -log M) did not affect phasic or tonic contractions to phenylephrine. The relatively nonselective α-adrenoceptor antagonist prazosin (7.5) shifted equally the potencies of phenylephrine at producing phasic and tonic contractions, with pK values of 8.85 and 8.83 (-log M), respectively. The α-adrenoceptor antagonist RS100329 (8.5) produced a significantly greater shift in phenylephrine potency for phasic (pK of 10.51) than tonic contractions (pK 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 α-adrenoceptors in responses of the rat portal vein to phenylephrine, but phasic responses involve predominantly α-adrenoceptors. Tonic responses may involve predominantly α-adrenoceptors and are at least partly mediated by mechanisms involving Rho kinase sensitive to fasudil.