Calcium dependency of the AT1-receptor mediated effects in the rat portal vein: influence of calcium antagonists.

The calcium dependency of AT1-receptor mediated contractions was studied in isolated rat portal vein preparations. The spontaneous phasic contractile force of the rat portal vein was increased (ED50 = 1.76 mmol/l) and the frequency of contractions decreased by raising the extracellular calcium concentration. The Ang II-induced rise in phasic contractile force (mediated by AT1-receptors, Zhang et al. 1993) proved most pronounced at 0.9 mmol/l of calcium chloride, but it was weaker at either lower or higher calcium concentrations. The maximal increases in the phasic contractile force induced by Ang II were 2.4 +/- 0.4, 14.8 +/- 0.9 and 5 +/- 0.5 mN at calcium concentrations of 0.5, 0.9 and 2.5 mmol/l, respectively. Calcium antagonists reduced at the lower and abolished at the higher concentrations (nifedipine 2 x 10(-8) or 10(-7) mol/l; verapamil 10(-7) or 5 x 10(-7) mol/l; diltiazem 3 x 10(-7) or 10(-6) mol/l) the spontaneous contractile force. All of these calcium antagonists caused a strong inhibition or suppression of the phasic contractions induced by Ang II. The rank order of potency was nifedipine > verapamil > diltiazem. Ang II (10(-6) mol/l) elicited a tonic contraction which was abolished by the AT1-receptor antagonist losartan 10(-6) mol/l but not by the AT2-receptor antagonist PD 123177 (10(-5) mol/l). Very high concentrations of nifedipine (10(-6) mol/l), verapamil (5 x 10(-6) mol/l) and diltiazem (5 x 10(-6) mol/l) almost suppressed the tonic effect evoked by the activation of AT1-receptors. In a nominally Ca2+ "free", EGTA-containing solution, a single supra-maximal concentration of Ang II (10(-6) mol/l) caused a transient contraction, also mediated by AT1-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)