Calcium channel blockade as a target for the cardiovascular effects induced by the 8 (17), 12E, 14-labdatrien-18-oic acid (labdane-302).
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.
de Oliveira
Aldeídia Pereira
AP
Laboratório de Tecnologia Farmacêutica, Universidade Federal da Paraíba, Cidade Universitária, Campus I, Caixa Postal 5009, CEP 58.051-900, João Pessoa, PB, Brazil.
Furtado
Fabíola Fialho
FF
da Silva
Marcelo Sobral
MS
Tavares
Josean F
JF
Mafra
Roberta Amaral
RA
Araújo
Demétrius Antonio Machado
DA
Cruz
Jader Santos
JS
de Medeiros
Isac Almeida
IA
D000818:Animals; D029061:Annonaceae / Q000737:chemistry*; D001464:Barium; D001794:Blood Pressure; D002121:Calcium Channel Blockers / Q000302:isolation & purification / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D024301:Plant Bark; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation
C515328:14-labdatrien-18-oic acid; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004224:Diterpenes; D004791:Enzyme Inhibitors; D001464:Barium; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester