Vardenafil, but not sildenafil or tadalafil, has calcium-channel blocking activity in rabbit isolated pulmonary artery and human washed platelets

dc.creatorToque, HA
dc.creatorTeixeira, CE
dc.creatorPriviero, FBM
dc.creatorMorganti, RP
dc.creatorAntunes, E
dc.creatorDe Nucci, G
dc.date2008
dc.dateJUN
dc.date2014-11-20T05:32:48Z
dc.date2015-11-26T17:15:23Z
dc.date2014-11-20T05:32:48Z
dc.date2015-11-26T17:15:23Z
dc.date.accessioned2018-03-29T00:03:38Z
dc.date.available2018-03-29T00:03:38Z
dc.identifierBritish Journal Of Pharmacology. Wiley-blackwell, v. 154, n. 4, n. 787, n. 796, 2008.
dc.identifier0007-1188
dc.identifierWOS:000256564500009
dc.identifier10.1038/bjp.2008.141
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/73182
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/73182
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/73182
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1282034
dc.descriptionBackground and purpose: Phosphodiesterase type-5 (PDE5) inhibitors constitute a novel and important therapeutic option for the treatment of pulmonary hypertension. The effects of the PDE5 inhibitors sildenafil, tadalafil and vardenafil on rabbit isolated pulmonary artery ring preparations and on intracellular Ca(2+) concentration of thrombin-stimulated human platelets were investigated. Experimental approach: Rabbit pulmonary artery rings were mounted in 10mL organ bath containing Krebs solution. Tissues were connected to force-displacement transducers, and changes in isometric force were recorded. Ca(2+) flux in human washed platelets was measured. Key results: Sildenafil, tadalafil and vardenafil (0.0001-10 mu M) concentration-dependently relaxed endothelium-intact and endothelium-denuded pulmonary artery rings. Endothelium denudation caused rightward shifts in the concentration response curves to sildenafil, tadalafil and vardenafil (9-, 12- and 123-fold, respectively). Incubation with N(omega)-nitro-L-arginine methyl ester (100 mu M) or ODQ (1H-[1,2,4] oxadiazolo [4,3,-a]quinoxalin-1-one) (10 mu M) caused similar reductions of PDE5-induced vasorelaxations in intact rings. Sildenafil and tadalafil did not affect the phenylephrine-induced contractions, whereas vardenafil reduced the maximal responses, and shifted the phenylephrine-induced contraction curves to the right in endothelium-denuded rings (5- and 19-fold for 1 and 10 mu M, respectively). Vardenafil (but neither sildenafil nor tadalafil) caused a marked rightward shift and a decrease of maximal contractile response to CaCl(2). Vardenafil, but neither sildenafil nor tadalafil, significantly reduced the Ca(2+) mobilization and Ca(2+) influx in thrombin-stimulated washed platelets. Conclusions and implications: Our results indicate that vardenafil, in contrast to sildenafil or tadalafil, also blocked Ca(2+) fluxes, thus enhancing its vasorelaxation of the pulmonary artery.
dc.description154
dc.description4
dc.description787
dc.description796
dc.languageen
dc.publisherWiley-blackwell
dc.publisherMalden
dc.publisherEUA
dc.relationBritish Journal Of Pharmacology
dc.relationBr. J. Pharmacol.
dc.rightsfechado
dc.rightshttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.sourceWeb of Science
dc.subjectpulmonary artery
dc.subjectPDE5 inhibitors
dc.subjectNO
dc.subjectcGMP
dc.subjectcalcium blockade
dc.subjectendothelium
dc.subjectrelaxation
dc.subjectErectile-dysfunction
dc.subjectNitric-oxide
dc.subjectType-5 Inhibitors
dc.subjectCyclic-gmp
dc.subjectHypertension
dc.subjectExpression
dc.subjectBlockers
dc.subjectEntry
dc.subjectPhosphodiesterases
dc.subjectMechanism
dc.titleVardenafil, but not sildenafil or tadalafil, has calcium-channel blocking activity in rabbit isolated pulmonary artery and human washed platelets
dc.typeArtículos de revistas


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