Muscarinic agonist properties involved in the hypotensive and vasorelaxant responses of rotundifolone in rats.
The acute cardiovascular effects of rotundifolone (ROT), the major constituent (63.5 %) of the essential oil of Mentha x villosa (OEMV), were tested in rats by using a combined (in vivo and in vitro) approach. ROT (1, 5, 10, 20 and 30 mg kg(-1) i. v.) induced a significant and dose-dependent hypotension and bradycardia in non-anaesthetized normotensive rats. The hypotensive effect was significantly attenuated by pre-treatment of the rats with atropine (2 mg kg(-1) i. v.) or L-NAME (20 mg kg(-1) i. v.). Furthermore, the bradycardic effect was abolished by atropine. In isolated rat atrial preparations, ROT (10, 100, 300 and 500 microg ml(-1)) produced concentration-related negative inotropic and chronotropic effects. In isolated intact aortic rings, increasing concentractions of ROT (0.3, 1, 10, 100, 300 and 500 microg ml(-1)) were able to antagonize the contractile effect of phenylephrine (1 microM) (IC50 = 184 +/- 6 microg ml(-1)). The smooth muscle-relaxant activity of ROT was inhibited by either removal of vascular endothelium, atropine (1 microM), L-NAME (100 and 300 microM) or indomethacin (10 microM) (IC50 values = 235 +/- 7, 247 +/- 8, 387 +/- 21, 723 +/- 75 and 573 +/- 38 microg ml(-1), respectively). These results suggest that rotundifolone markedly lowers arterial pressure and heart rate in non-anaesthetized animals. The hypotensive action of rotundifolone can be a consequence of a decrease in heart rate and peripheral vascular resistance, probably due to a non-selective muscarinic receptor stimulation.
Guedes
D N
DN
Laboratório de Tecnologia Farmacêutica, Universidade Federal da Paraíba, João Pessoa, PB, Brazil.
Silva
D F
DF
Barbosa-Filho
J M
JM
Medeiros
I A
IA
D000818:Animals; D006325:Heart Atria / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007022:Hypotension / Q000503:physiopathology; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D008297:Male; D027541:Mentha / Q000737:chemistry*; D039821:Monoterpenes / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D010946:Plants, Medicinal / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D039821:Monoterpenes; D018721:Muscarinic Agonists; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C467828:rotundifolone