Endothelium-dependent, nitric oxide-mediated inhibition of angiotensin II-induced contractions in rabbit aorta.
The role of endothelium in angiotensin II-induced contractions of the rabbit aorta and the mechanism involved were investigated. Destruction of the endothelium significantly shifted the concentration-response curve for angiotensin II to the left in a non-parallel manner and enhanced the maximal response. The EC50 and Emax values obtained from the rings with and without functional endothelium were 2.44 +/- 0.13 x 10(-9) M, 4.50 +/- 0.45 g and 1.21 +/- 0.14 x 10(-9) M (n = 8, P < 0.05), 5.73 +/- 0.55 g (n = 8, P < 0.05), respectively. Indomethacin (10(-5) M) did not significantly alter the concentration-dependent response to angiotensin II in the presence of endothelium. Three inhibitors of nitric oxide synthase (NG-monomethyl-L-arginine; NG-nitro-L-arginine, and NG-nitro-L-arginine methyl ester) at 10(-4) M caused a similar endothelium-dependent potentiation of angiotensin II-induced contractions in the aortic rings with, but not in those without endothelium. These effects were reversed by L-arginine (3 x 10(-3) M) but not by D-arginine (3 x 10(-3) M). Angiotensin II in a concentration range of 10(-16) to 10(-6) M did not relax the endothelium-intact rings precontracted with phenylephrine (2 x 10(-7) M). In the presence of endothelium, the angiotensin II subtype 2 receptor antagonist, 1-[(4-amino-3-methylphenyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro- 1H- imidazol[4,5-C]pyridine-6-carboxylic acid (PD 123177), caused neither relaxation of the rings precontracted with phenylephrine nor alteration of the concentration-response curve for angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)
Zhang
J
J
Department of Pharmacotherapy, University of Amsterdam, Netherlands.
Van Meel
J C
JC
Pfaffendorf
M
M
Zhang
J
J
Van Zwieten
P A
PA
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019335:Nitroarginine; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D019323:omega-N-Methylarginine
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D011725:Pyridines; D000804:Angiotensin II; C066253:PD 123177; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin