Cardiovascular effects of trans-dehydrocrotonin, a diterpene from Croton cajucara in rats.
Previous studies have established the gastroprotective, hypoglycemic, and hypolipidemic effects of trans-dehydrocrotonin (t-DCTN), a major diterpene isolated from the Amazon medicinal plant Croton cajucara. This study aims to examine the potential effects of t-DCTN on hemodynamic parameters that include resting arterial blood pressure and heart rate in vivo, and on left atrial force, spontaneous beating atria, and aortic rings of rats in vitro. Intravenous bolus injections of t-DCTN (5, 10, or 15 mg/kg) to urethane anesthetized normotensive rats reduced the mean arterial pressure and heart rate in a dose-dependent manner. The hypotensive effect of t-DCTN (10 mg/kg) appears not mediated through effects on the muscarinic cholinergic receptor, beta-adrenoceptor, or ganglionic blockade, for it was not affected by atropine, propranolol, or hexamethonium but was abolished by N(w)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor. The diterpene t-DCTN showed no significant influence on inotropism. In isolated rat aortic rings with intact or denuded endothelium, t-DCTN relaxed the tonic contraction induced by phenylephrine (1 microM). Its vasorelaxant effect seen at smaller concentrations in endothelium intact preparations was, however, abolished in endothelium denuded or in l-NAME treated tissues. These data indicate the hypotensive and bradycardia effects of t-DCTN, possibly related in part to the release of nitric oxide and in part to direct effects on vascular smooth muscle, and cardiac pacemaker activity.
Departamento de Fisiologia e Farmacologia, FM, Universidade Federal do Ceará-UFC, Rua Cel Nunes de Melo 1127, Porangabussu, Caixa Postal-3157, 60430-270 Fortaleza, Ceará, Brazil.
Regilane M
RM
Silva
Francisco A
FA
Oliveira
Karina M A
KM
Cunha
Juliana L
JL
Maia
Maria Aparecida M
MA
Maciel
Angelo C
AC
Pinto
Nilberto R F
NR
Nascimento
Flavia A
FA
Santos
Vietla S N
VS
Rao
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D029802:Croton / Q000737:chemistry*; D045785:Diterpenes, Clerodane / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006584:Hexamethonium Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D045785:Diterpenes, Clerodane; D004791:Enzyme Inhibitors; D006584:Hexamethonium Compounds; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C103060:dehydrocrotonin; D010656:Phenylephrine; D001285:Atropine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019331:NG-Nitroarginine Methyl Ester