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

Vascul Pharmacol. 2006 May;44(5):338-44. doi: 10.1016/j.vph.2006.01.009. Epub 2006 Mar 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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