Vasorelaxation induced by methyl cinnamate, the major constituent of the essential oil of<i>Ocimum micranthum</i>, in rat isolated aorta

Abstract

The aim of the present study was to investigate the vascular effects of the E-isomer of methyl cinnamate (E-MC) in rat isolated aortic rings and the putative mechanisms underlying these effects. At 1-3000 μmol/L, E-MC concentration-dependently relaxed endothelium-intact aortic preparations that had been precontracted with phenylephrine (PHE; 1 μmol/L), with an IC50 value (geometric mean) of 877.6 μmol/L (95% confidence interval (CI) 784.1-982.2 μmol/L). These vasorelaxant effects of E-MC remained unchanged after removal of the vascular endothelium (IC50 725.5 μmol/L; 95% CI 546.4-963.6 μmol/L) and pretreatment with 100 μmol/L N(G) -nitro-l-arginine methyl ester (IC50 749.0 μmol/L; 95% CI 557.8-1005.7 μmol/L) or 10 μmol/L 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (IC50 837.2 μmol/L; 95% CI 511.4-1370.5 μmol/L). Over the concentration range 1-3000 μmol/L, E-MC relaxed K(+) -induced contractions in mesenteric artery preparations (IC50 314.5 μmol/L; 95% CI 141.9-697.0 μmol/L) with greater potency than in aortic preparations (IC50 1144.7 μmol/L; 95% CI 823.2-1591.9 μmol/L). In the presence of a saturating contractile concentration of K(+) (150 mmol/L) in Ca(2+) -containing medium combined with 3 μmol/L PHE, 1000 μmol/L E-MC only partially reversed the contractile response. In contrast, under similar conditions, E-MC nearly fully relaxed PHE-induced contractions in aortic rings in a Ba(2+) -containing medium. In preparations that were maintained under Ca(2+) -free conditions, 600 and 1000 μmol/L E-MC significantly reduced the contractions induced by exogenous Ca(2+) or Ba(2+) in KCl-precontracted preparations, but not in PHE-precontracted preparations (in the presence of 1 μmol/L verapamil). In addition, E-MC (1-3000 μmol/L) concentration-dependently relaxed the contractions induced by 2 mmol/L sodium orthovanadate. Based on these observations, E-MC-induced endothelium-independent vasorelaxant effects appear to be preferentially mediated by inhibition of plasmalemmal Ca(2+) influx through voltage-dependent Ca(2+) channels. However, the involvement of a myogenic mechanism in the effects of E-MC is also possible.