Characterization of the angiotensin II-receptor subtype in the longitudinal smooth muscle of the rat portal vein.
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 123,177, 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Zhang
J S
JS
Department of Pharmacotherapy, Academic Medical Centre, University of Amsterdam, The Netherlands.
Van Meel
J C
JC
Pfaffendorf
M
M
Van Zwieten
P A
PA
D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D004229:Dithiothreitol / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000648:ultrastructure*; D011169:Portal Vein / Q000648:ultrastructure*; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000145:classification*; D012680:Sensitivity and Specificity
D057911:Angiotensin Receptor Antagonists; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D004229:Dithiothreitol; D007213:Indomethacin