Calcium channel blockade as a target for the cardiovascular effects induced by the 8 (17), 12E, 14-labdatrien-18-oic acid (labdane-302)

Vascular Pharmacology
Aldeídia Pereira de OliveiraIsac Almeida de Medeiros

Abstract

The cardiovascular effects induced by labdane-302, a diterpene isolated from the stems of Xylopia langsdorffianna St. Hill and Tull, were evaluated in male Wistar rats. In normotensive, conscious animals, labdane-302 produced dose-dependent hypotension and tachycardia. These effects were significantly attenuated after pre-treatment with L-NAME (20 mg/kg, i.v.). In isolated mesenteric artery rings, labdane-302 (10(-10)-10(-4)M) elicited concentration-dependent relaxation of phenylephrine-induced contractions (IC50 = 5.4 +/- 1.4 microM). Endothelium removal, and pre-treatment with L-NAME (100 microM) or indomethacin (10 microM) caused significant reductions in sensitivity. Labdane-302 also caused concentration-dependent relaxation in arterial rings pre-contracted with high extracellular KCl (80 mM). In Ca2+-free depolarized preparations, labdane-302 inhibited contractions produced by cumulative increases in extracellular Ca2+ concentration. In GH3 cells, labdane-302 (100 microM) inhibited whole-cell L-type Ca2+ currents by approximately 50%. These results demonstrate that labdane-302 causes hypotension through peripheral vasodilation, mediated in part by NO and PGI2 and by blockade of Ca2+ entry through L-type Ca2+ channels.

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Citations

Jun 21, 2014·Journal of Ayurveda and Integrative Medicine·Poonam VermaAjudhia N Kalia
Oct 1, 2008·Naunyn-Schmiedeberg's Archives of Pharmacology·Marcos Antônio A MedeirosJader S Cruz
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Jun 2, 2009·Journal of Ethnopharmacology·Oluwatosin A AdaramoyeIsac A Medeiros
May 8, 2007·Vascular Pharmacology·Daniela Z DimitrovaDessislava B Duridanova
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