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Acta Pharmacol Sin ; 36(11): 1318-26, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26564314

RESUMEN

AIM: Brazilin is one of the major constituents of Caesalpinia sappan L with various biological activities. This study sought to investigate the vasorelaxant effect of brazilin on isolated rat thoracic aorta and explore the underlying mechanisms. METHODS: Endothelium-intact and -denuded aortic rings were prepared from rats. The tension of the preparations was recorded isometrically with a force displacement transducer connected to a polygraph. The phosphorylation levels of ERK1/2 and myosin light chain (MLC) were analyzed using Western blotting assay. RESULTS: Application of brazilin (10-100 µmol/L) dose-dependently relaxed the NE- or high K(+)-induced sustained contraction of endothelium-intact aortic rings (the EC50 was 83.51±5.6 and 79.79±4.57 µmol/L, respectively). The vasorelaxant effect of brazilin was significantly attenuated by endothelium removal or by pre-incubation with L-NAME, methylene blue or indomethacin. In addition, pre-incubation with brazilin dose-dependently attenuated the vasoconstriction induced by KCl, NE or Ang II. Pre-incubation with brazilin also markedly suppressed the high K(+)-induced extracellular Ca(2+) influx and NE-induced intracellular Ca(2+) release in endothelium-denuded aortic rings. Pre-incubation with brazilin dose-dependently inhibited the NE-stimulated phosphorylation of ERK1/2 and MLC in both endothelium-intact and -denuded aortic rings. CONCLUSION: Brazilin induces relaxation in rat aortic rings via both endothelium-dependent and -independent ways as well as inhibiting NE-stimulated phosphorylation of ERK1/2 and MLC. Brazilin also attenuates vasoconstriction via blocking voltage- and receptor-operated Ca(2+) channels.


Asunto(s)
Aorta/efectos de los fármacos , Benzopiranos/farmacología , Endotelio Vascular/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacología , Animales , Aorta/fisiología , Benzopiranos/aislamiento & purificación , Caesalpinia/química , Endotelio Vascular/fisiología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Masculino , Cadenas Ligeras de Miosina/metabolismo , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Fosforilación/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Vasodilatadores/aislamiento & purificación
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