Muscarinic Agonist Properties Involved in the Hypotensive and Vasorelaxant Responses of Rotundifolone in Rats

Abstract

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 μg 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 μg ml^-1) were able to antagonize the contractile effect of phenylephrine (1 μM) (IC₅₀ = 184 ± 6 μg ml^-1). The smooth muscle-relaxant activity of ROT was inhibited by either removal of vascular endothelium, atropine (1 μM), L-NAME (100 and 300 μM) or indomethacin (10 μM) (IC₅₀ values = 235 ± 7, 247 ± 8, 387 ± 21, 723 ± 75 and 573 ± 38 μg 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.

Rotundifolone - hypotension - muscarinic receptor - aortic rings - nitric oxide - vasodilation

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