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Angiotensin II-Induced Relaxation of Anococcygeus Smooth Muscle via Desensitization of AT1 Receptor, and Activation of AT2 Receptor Associated with Nitric-Oxide Synthase Pathway

By Márcio A. F. De Godoy, Ana Maria De Oliveira and Satish Rattan

Abstract

We evaluated the role of receptor desensitization, activation of AT2 receptors, and enzymatic degradation of angiotensin II (Ang II) by amino/neutral endopeptidases in rat anococcygeus smooth muscle (ASM) relaxation. Ang II (0.3 nM to 10 M) produced contractions (Emax 21.50 5.73%) followed by passive relax-ations (Emax reduced to 9.08 2.55%). Contractions were inhib-ited (Emax 13.67 2.03%) by losartan (0.1 M; AT1 antagonist) but not by PD123,319 [S-()-1-([4-(dimethylamino)-3-methylphe-nyl]methyl)-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo(4,5-c)pyridine-6-carboxylic acid] (0.1 M; AT2 antagonist). Con-versely, the passive relaxation was inhibited (Emax 18.00 3.45%) by PD123,319 but not by losartan. Ang II (0.3 M to 100 M) produced initial contractions (Emax 11.49 9.39%) fol-lowed by active relaxations [Imax (maximum inhibition elicited b

Year: 2004
DOI identifier: 10.1124/jpet.104.069856
OAI identifier: oai:CiteSeerX.psu:10.1.1.1015.5401
Provided by: CiteSeerX
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