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

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

Download PDF:
_{Sorry, we are unable to provide the full text but you may find it at the following location(s):}

http://jpet.aspetjournals.org/... (external link)

http://jpet.aspetjournals.org/... (external link)

http://citeseerx.ist.psu.edu/v... (external link)