Mechanism of action of angiotensin II on excitation-contraction coupling in the rat portal vein.

1 The action of angiotensin II (At II) has been studied on the electrical and mechanical activity of the vascular smooth muscle of the rat portal vein.2 At low concentrations (between 5 x 10(-10) and 10(-9) M) At II induces an acceleration of spontaneous action potential (AP) discharge without change in the resting membrane potential. The frequency and size of the associated contractions are simultaneously augmented. Under these conditions the size of the spikes is not affected, thus suggesting that At II triggers the release of Ca(2+) from internal stores.3 The increase in AP discharge rate produced by low concentrations of At II results from an acceleration of the pacemaker potential. Furthermore, in the presence of 10 mM tetraethylammonium (TEA), there is an acceleration of the repolarizing phase of AP.4 Ouabain (10(-3) M) inhibits the increase in rhythmic activity induced by low concentrations of At II (in the presence of 10 mM TEA), thus suggesting that the Na-K pump is directly or indirectly involved in this action of the peptide.5 At higher concentrations, At II produces a concentration-dependent depolarization with an EC(50) of 1.2 x 10(-8) M and a maximum of 10(-7) M. The associated contraction has an EC(50) of 3.3 x 10(-8) M and a maximum of 3 x 10(-7) M.6 Ouabain (3 x 10(-3) M) depolarizes the cell membrane. Under these conditions, At II (10(-7) M) has a slight depolarizing effect, but it still produces a large tonic contraction.7 It is concluded, that At II acts on different steps of excitation-contraction coupling, depending on the concentration. At low levels, the peptide mainly accelerates spike discharge, through a mechanism involving the Na-K pump. At higher concentrations, At II depolarizes the cell membrane. The contraction is then activated by the influx of Ca(2+) due to secondary AP discharge and the release of Ca(2+) from intracellular stores. Pharmacomechanical coupling has an important role in the triggering of contractions both at high and at low concentrations of At II.