EFFECTS OF DILTIAZEM ON PHASIC AND TONIC ACTIVITY IN RAT PORTAL VEIN

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Abstract
The effects of the Ca2+ entry blocking drug diltiazem were 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 UK14304 [5-bromo-N-(4,5-dihydro-1,4-imidazol-2-yl)-6-quinoxalinamine] or TL99 [2(N,N-dimethyl)amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene] 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.-adrenoceptor agonist (NA [norepinephrine]) or of tonic responses evoked by high concentrations of K+ or PE. The non-stimulated phasic activity of the portal vein was antagonized by diltiazem at higher concentrations only. Evidently, in the rat portal vein, phasic or tonic activity are associated with different Ca2+-gating mechanisms. 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.