Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/73182
Type: Artigo de periódico
Title: Vardenafil, but not sildenafil or tadalafil, has calcium-channel blocking activity in rabbit isolated pulmonary artery and human washed platelets
Author: Toque, HA
Teixeira, CE
Priviero, FBM
Morganti, RP
Antunes, E
De Nucci, G
Abstract: Background 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.
Subject: pulmonary artery
PDE5 inhibitors
NO
cGMP
calcium blockade
endothelium
relaxation
Country: EUA
Editor: Wiley-blackwell
Rights: fechado
Identifier DOI: 10.1038/bjp.2008.141
Date Issue: 2008
Appears in Collections:Unicamp - Artigos e Outros Documentos

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