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

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.

• Authors: Aldeídia Pereira de Oliveira, Fabíola Fialho Furtado, Marcelo Sobral da Silva, Josean F Tavares, Roberta Amaral Mafra, Demétrius Antonio Machado Araújo, Jader Santos Cruz, Isac Almeida de Medeiros
• Journal: Vascular pharmacology (Vascul Pharmacol) Vol. 44 Issue 5 Pg. 338-44 (May 2006) ISSN: 1537-1891 [Print] United States
• PMID: 16524785 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 14-labdatrien-18-oic acid
• Calcium Channel Blockers
• Calcium Channels, L-Type
• Diterpenes
• Enzyme Inhibitors
• Barium
• Nitric Oxide Synthase
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Annonaceae (chemistry)
• Barium
• Blood Pressure
• Calcium Channel Blockers (isolation & purification, pharmacology)
• Calcium Channels, L-Type (drug effects, metabolism)
• Diterpenes (isolation & purification, pharmacology)
• Dose-Response Relationship, Drug
• Endothelium, Vascular (drug effects, metabolism)
• Enzyme Inhibitors (pharmacology)
• Heart (drug effects)
• Heart Rate
• Male
• Mesenteric Arteries (drug effects, metabolism)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide Synthase (antagonists & inhibitors, metabolism)
• Plant Bark
• Rats
• Rats, Wistar
• Vasodilation