title: Calcium dependency of the AT1-receptor mediated effects in the rat portal vein: influence of calcium antagonists.
abstract: 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)
authors.affiliation: Department of Pharmacotherapy, University of Amsterdam, The Netherlands.
authors.forename: J S
authors.initials: JS
authors.lastname: Zhang
authors.forename: J C
authors.initials: JC
authors.lastname: Van Meel
authors.forename: M
authors.initials: M
authors.lastname: Pfaffendorf
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: P A
authors.initials: PA
authors.lastname: Van Zwieten
mesh_terms: D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D011169:Portal Vein / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000502:physiology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D002121:Calcium Channel Blockers; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000803:Angiotensin I; D002118:Calcium