The semi-synthetic kaurane ent-16 alpha-methoxykauran-19-oic acid induces vascular relaxation and hypotension in rats
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Data
2011-06-25
Autores
Hipolito, Ulisses V.
Rocha, Juliana T.
Palazzin, Nathalia B.
Rodrigues, Gerson Jhonatan [UNESP]
Crestani, Carlos Cesar [UNESP]
Correa, Fernando M.
Bonaventura, Daniella
Ambrosio, Sergio R.
Bendhack, Lusiane M.
Resstel, Leonardo B.
Título da Revista
ISSN da Revista
Título de Volume
Editor
Elsevier B.V.
Resumo
The present work investigates the mechanisms involved in the vasorelaxant effect of ent-16 alpha-methoxykauran-19-oic acid (KA-OCH(3)), a semi-synthetic derivative obtained from the kaurane-type diterpene ent-kaur-16-en-19-oic acid (kaurenoic acid). Vascular reactivity experiments were performed in aortic rings isolated from male Wistar rats using standard muscle bath procedures. The cytosolic calcium concentration ([Ca(2+)]c) was measured by confocal microscopy using the fluorescent probe Fluo-3 AM. Blood pressure measurements were performed in conscious rats. KA-OCH(3) (10,50 and 100 mu mol/l) inhibited phenylephrine-induced contraction in either endothelium-intact or endothelium-denuded rat aortic rings. KA-OCH(3) also reduced CaCl(2)-induced contraction in a Ca(2+)-free solution containing KCl (30 mmol/l) or phenylephrine (0.1 mu mol/l). KA-OCH(3) (0.1-300 mu mol/l) concentration-dependently relaxed endothelium-intact and endothelium-denuded aortas pre-contracted with either phenylephrine or KCl, to a greater extent than kaurenoic acid. Moreover, a Ca(2+) mobilisation study showed that KA-OCH(3) (100 mu mol/l) inhibited the increase in Ca(2+) concentration in smooth muscle and endothelial cells induced by phenylephrine or KCl. Pre-incubation of intact or denuded aortic rings with N(G)-nitro-L-arginine methyl ester (L-NAME, 100 mu mol/l), 7-nitroindazole (100 mu mol/l), wortmannin (0.5 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 KA-OCH(3) concentration-response curve. Intravenous administration of KA-OCH(3) (1-10 mg/kg) reduced mean arterial blood pressure in normotensive rats. Collectively, our results show that KA-OCH(3) induces vascular relaxation and hypotension. The mechanisms underlying the cardiovascular actions of KA-OCH(3) involve blockade of Ca(2+) influx and activation of the NO-cGMP pathway. (C) 2011 Elsevier B.V. All rights reserved.
Descrição
Palavras-chave
ent-16 alpha-methoxykauran-19-oic acid, Relaxation, Rat aorta, Diterpene, Ca(2+)
Como citar
European Journal of Pharmacology. Amsterdam: Elsevier B.V., v. 660, n. 2-3, p. 402-410, 2011.