Characterization of the angiotensin II-receptor subtype in the longitudinal smooth muscle of the rat portal vein |
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| Authors: | J. S. Zhang J. C. A. Van Meel M. Pfaffendorf P. A. Van Zwieten |
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| Affiliation: | (1) Department of Pharmacotherapy, Academic Medical Centre, University of Amsterdam, Meibergdreef 15, NL-1105 AZ Amsterdam, The Netherlands;(2) Dr. Karl Thomae GmbH, Division of Cardiovascular Pharmacology, Birkendorferstrasse 65, W-7950 Biberach/Riss, Germany |
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| Abstract: | Summary The purpose of the present study was to identify the angiotensin II-receptor subtype involved in the enhancement of the amplitude of the phasic contractions by angiotensin II in the isolated rat portal vein preparation.At an extracellular Ca2+ concentration of 0.9 mmol/l and a K+ concentration of 4 mmol/l, angiotensin II induced concentration-dependent increases in the amplitude of the phasic contractions. The enhancement of phasic contraction amplitude caused by angiotensin II was not significantly altered by pretreatment of the rat portal vein with indomethacin 10–5 mol/l or nitro-L-arginine 10–4 mol/l, indicating that neither prostaglandins nor the endothelium derived-relaxing factor (NO) are involved. Losartan (DuP 753), a nonpeptide selective AT1-receptor antagonist, concentration-dependently shifted the concentration-response curve for the effect of angiotensin II on the amplitude of the contractions to the right, without reducing the maximal response (pA2 = 8.6, slope = 0.98), thus suggesting competitive antagonism at the level of AT1-receptors. By contrast, PD 123177, a nonpeptide selective AT2-receptor antagonist, even at 10–5 mol/l, caused no significant change of the phasic myogenic response to angiotensin II, indicating the absence of AT2-receptor involvement. Dithiothreitol, a disulfide-reducing agent which is known to inactivate AT1-receptors in various tissues, markedly inhibited (3 mmol/l) or even abolished (5 mmol/l) the contractile response of the rat portal vein to angiotensin II, supporting the conclusion that these receptors can be classified as AT1-receptors.In conclusion, the receptor subtype mediating the angiotensin II-induced potentiation of the spontaneous phasic contractions in the rat portal vein appears to belong to the AT1-receptor subtype.Preliminary data were presented at the Spring Meeting of the German Pharmacological Society, Mainz, 1992Correspondence to J. S. Zhang at the above address |
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| Keywords: | Angiotensin II-receptor Dithiothreitol Nonpeptide angiotensin II-receptor antagonists Rat portal vein |
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