Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/102745
Type: Artigo de evento
Title: Vasorelaxing Effect Of Bay 41-2272 In Rat Basilar Artery: Involvement Of Cgmp-dependent And Independent Mechanisms
Author: Teixeira C.E.
Priviero F.B.M.
Todd Jr. J.
Webb R.C.
Abstract: Decreases in intrinsic NO cause cerebral vasospasms because of the dysregulation of cGMP formation by NO-mediated pathways. Because 5-cyclopropyl-2-{1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl} pyrimidin-4-ylamine (BAY 41-2272) is a potent soluble guanylyl cyclase (sGC) stimulator in an NO-independent manner, this study aimed to investigate the mechanisms underlying the relaxant effects of BAY 41-2272 in the rat basilar artery. BAY 41-2272 (0.0001 to 1 μmol/L) induced relaxations in a concentration-dependent manner, with pEC50 values of 8.13±0.03 and 7.63±0.05 in intact and denuded rings, respectively. The sGC inhibitor 1H-[1,2,4] oxadiazolo [4,3,-a]quinoxalin-1-one (ODQ) markedly displaced the curve for BAY 41-2272 to the right in intact or denuded rings (≈10-fold). The NO synthesis inhibitor NG-nitro-L-arginine methyl ester caused a rightward shift in the curve for BAY 41-2272 (4-fold), whereas the phosphodiesterase type 5 inhibitor sildenafil enhanced BAY 41-2272-induced relaxations (3- to 4-fold). The Na+-K+-ATPase inhibitor ouabain caused 3-fold rightward shifts in the curves for BAY 41-2272. Ca 2+-induced contractions in K+ depolarized rings were significantly attenuated by BAY 41-2272 in an ODQ-insensitive manner. The NO donor glyceryl trinitrate and BAY 41-2272 caused rightward shifts in the contractile responses to serotonin. Their coincubation caused a synergistic inhibition of serotonin-induced contractions. BAY 41-2272 and glyceryl trinitrate increased cGMP levels (but not cAMP) by 10-fold and 4-fold above baseline, respectively, in an ODQ-sensitive manner. cGMP levels increased by 50-fold after coincubation. BAY 41-2272 potently relaxes the rat basilar artery in a synergistic fashion with NO. Targeting the sGC with selective activators, such as BAY 41-2272, may represent a new therapy to treat cerebrovascular disease. © 2006 American Heart Association, Inc.
Editor: 
Rights: fechado
Identifier DOI: 10.1161/01.HYP.0000199914.36936.1b
Address: http://www.scopus.com/inward/record.url?eid=2-s2.0-33644981623&partnerID=40&md5=74d8e55fca852585a596e9b2cddf2d1b
Date Issue: 2006
Appears in Collections:Unicamp - Artigos e Outros Documentos

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