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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Mechanisms underlying the vasorelaxant action of the pimarane ent-8(14),15-pimaradien-3 beta-ol in the isolated rat aorta

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Autor(es):
Hipolito, Ulisses V. [1, 2] ; Rodrigues, Gerson J. [3, 1] ; Lunardi, Claure N. [3, 4] ; Bonaventura, Daniella [3] ; Ambrosio, Sergio R. [5] ; de Oliveira, Ana M. [3] ; Bendhack, Lusiane M. [3] ; da Costa, Fernando B. [6] ; Tirapelli, Carlos R. [2]
Número total de Autores: 9
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Dept Pharmacol, Fac Med Ribeirao Preto, BR-14040902 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Dept Psychiat Nursing & Human Sci, Pharmacol Lab, Coll Nursing Ribeirao Preto, BR-14040902 Ribeirao Preto, SP - Brazil
[3] Univ Sao Paulo, Dept Chem & Phys, Pharmacol Lab, Fac Pharmaceut Sci, BR-14040902 Ribeirao Preto, SP - Brazil
[4] UnB, Fac Ceilandia, Brasilia, DF - Brazil
[5] Univ Franca, Franca, SP - Brazil
[6] Univ Sao Paulo, Dept Pharmaceut Sci, Pharmacol Lab, Fac Pharmaceut Sci, BR-14040902 Ribeirao Preto, SP - Brazil
Número total de Afiliações: 6
Tipo de documento: Artigo Científico
Fonte: European Journal of Pharmacology; v. 616, n. 1-3, p. 183-191, AUG 15 2009.
Citações Web of Science: 15
Resumo

Pimarane-type diterpenes were described to exert antispasmodic and relaxant activities. Based on this observation we hypothesized that the diterpene ent-8(14),15-pimaradien-3 beta-ol (PA-3 beta-ol) induced vascular relaxation. With this purpose, the present work investigates the mechanisms involved in the vasorelaxant effect of the pimarane-type diterpene PA-3 beta-ol. Vascular reactivity experiments, using standard muscle bath procedures, were performed in isolated aortic rings from male Wistar rats. Cytosolic calcium concentration ({[}Ca(2+)]c) was measured by confocal microscopy using the fluorescent probe Fluo-3AM. PA-3 beta-ol (10, 50 and 100 mu mol/l) inhibited phenylephrine and KCl-induced contraction in either endothelium-intact or denuded rat aortic rings. PA-3 beta-ol also reduced CaCl(2)-induced contraction in Ca(2+)-free solution containing KCl (30 mmol/l) or phenylephrine (0.1 mu mol/l). PA-3 beta-ol (1-300 mu mol/l) concentration dependently relaxed phenylephrine-pre-contracted rings with intact or denuded endothelium. The diterpene also relaxed KCl-pre-contracted rings with intact or denuded endothelium. Moreover, Ca(2+) mobilization study showed that PA-3 beta-ol (100 mu mol/l) and verapamil (1 mu mol/l) inhibited the increase in Ca(2+)-concentration in smooth muscle and endothelial cells induced by phenylephrine (10 mu mol/l) or KCl (60 mmol/l). Pre-incubation of intact or denuded aortic rings with N(G)-nitro-L-arginine methyl ester (L-NAME, 100 mu mol/l) and 1H-{[}1,2,4] Oxadiazolo{[}4,3-a]quinoxalin-1-one (ODQ 1 mu mol/l) produced a rightward displacement of the PA-3 beta-ol concentration-response curves. On the other hand, 7-nitroindazole (100 mu mol/l), 1400 W (1 mu mol/l), indomethacin (10 mu mol/l) and tetraethylammonium (1 mmol/l) did not affect PA-3 beta-ol-induced relaxation. Collectively, our results provide evidence that the effects elicited by PA-3 beta-ol involve extracellular Ca(2+) influx blockade. Its effects are also partly mediated by the activation of NO-cGMP pathway. (C) 2009 Elsevier B.V. All rights reserved. (AU)

Processo FAPESP: 06/52611-0 - Estudo do efeito do pimarano ent-8(14), 15-pimaradien-3b-ol sobre a reatividade vascular de arteria aorta isolada e pressao arterial de ratos normotensos e hipertensos.
Beneficiário:Ulisses Vilela Hipólito
Linha de fomento: Bolsas no Brasil - Iniciação Científica