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|Title:||Ethyl rosmarinate relaxes rat aorta by an endothelium-independent pathway|
|Keywords:||Pharmacology, Toxicology and Pharmaceutics|
|Abstract:||© 2015 Elsevier B.V. Ethyl rosmarinate is an ester derivative of rosmarinic acid, a major constituent of Hyptis suaveolens. The present study investigated the vasorelaxant mechanism of ethyl rosmarinate in isolated rat aortic rings using an organ bath system. Ethyl rosmarinate (0.1 μM-3 mM) produced concentration-dependent relaxation in aortic rings pre-contracted with phenylephrine (10 μM), exhibiting a pD2value of 4.56±0.08 and an Emaxvalue of 93.82±5.00% (in endothelium-intact rings), as well as a pD2value of 4.42±0.05 and an Emaxvalue of 92.10±3.78% (in endothelium-denuded rings). In the endothelium-denuded rings, the vasorelaxant effect of ethyl rosmarinate was reduced by only 4-aminopyridine (1 mM); however, this was not the case with tetraethylammonium (5 mM), glibenclamide (10 μM), barium chloride (1 mM), and 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (ODQ, 1 μM). Ethyl rosmarinate also reduced the contraction induced by phenylephrine (10 μM) and caffeine (20 mM) in a Ca2+-free solution, and inhibited the contraction induced by increasing extracellular Ca2+influx, which was induced by KCl (80 mM). Ethyl rosmarinate (10 μM) inhibits concentration-response curves for phenylephrine, while in the same concentration of ethyl rosmarinate has no effect on contractions induced by increasing concentrations of calcium in the presence of high extracellular potassium. Our results suggests that ethyl rosmarinate induces relaxation in aortic rings via an endothelium-independent pathway, which involves the opening of voltage-gated potassium (Kv) channels and the blockade of both Ca2+release from intracellular stores and extracellular Ca2+influx. Moreover, ethyl-rosmarinate acts on the extracellular Ca2+influx inhibition by interacting with voltage-operated calcium channels (VOCCs) and receptor-operated calcium channels (ROCCs).|
|Appears in Collections:||CMUL: Journal Articles|
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