Effects of diltiazem on phasic and tonic activity in rat portal vein

The effects of the Ca2+ entry blocking drug, diltiazem, have been evaluated in the rat isolated portal vein, against phasic or tonic responses induced by a range of agonists. Diltiazem was a potent antagonist of phasic responses induced by low concentrations of K+, tetraethylammonium (TEA), the selective alpha 2-adrenoreceptor agonists UK 14304 or TL99 and angiotensin II (AII). Diltiazem was significantly less potent as an antagonist of phasic responses induced by the selective alpha 1-adrenoreceptor agonists phenylephrine (PE) or methoxamine (ME) or the non-selective alpha-adrenoreceptor agonist (NA), or of tonic responses evoked by high concentrations of K+, or PE. The non-stimulated phasic activity of the portal vein was antagonised by diltiazem at higher concentrations only. It is concluded that in the rat portal vein, phasic or tonic activity are associated with different Ca2+-gating mechanisms. It is considered that these differences could represent different Ca2+-channels, different rates of activation or deactivation of the channels, or involve other sources of activator Ca2+ than extracellular Ca2+. The alpha 2-adrenoreceptor subtype may be functionally linked with a voltage dependent Ca2+-channel to cause phasic responses in this preparation.