Inhibition of As(III) and Hg(II) caused aortic hypercontraction by eugenol, linalool and carvone

Abstract

Acute and chronic exposure to arsenic and mercury is known to produce vasoconstriction. There is, however, no clarity concerning the pathways leading to this increased contraction. In this study we elicit and compare maximum contractility of rat aortas under resting conditions in the presence of arsenic and mercury, and delineate pathways mediating this effect. Phenylephrine (PE) induced hypercontraction of 37% and 32% were obtained when isolated aortic segments were exposed to 25 µM As(III) and 6 nM Hg(II), respectively. Isometric contraction measurements in presence of apocynin, verapamil and sodium nitroprusside indicates that the major causes of increased contraction are reactive oxygen species (ROS) and depletion of nitric oxide (NO). Calcium influx plays a minor role in arsenic and mercury caused hypercontraction. In unexposed aorta, eugenol causes relaxation by inhibiting ROS and elevating NO, linalool by blocking voltage dependent calcium channel (VDCC) and elevating NO, and carvone by blocking calcium influx through VDDC. Since the arsenic and mercury hypercontraction is mediated by increased ROS and depleted NO, we hypothesize that molecules which neutralize ROS or elevate NO will be better ameliorators. In line with this argument, we found eugenol to be the best ameliorator of arsenic and mercury hypercontraction followed by linalool and carvone.

Cardiovascular Activity of the Chemical Constituents of Essential Oils

“…Its enantiomer is a constituent of dill and caraway oils [ 59 ]. To investigate the effect of carvone on conductance arteries, Kundu et al [ 60 ] demonstrated that this terpenoid was capable of promoting vasorelaxation on pre-contracted aortic rings, even when the artery was exposed to metals (arsenic and mercury). The antioxidant proprieties of carvone contributed to this vasorelaxant effect.…”

“…This phenylpropanoid is used as an ingredient in cosmetics, perfumes, and pharmaceutical and dental preparations [ 62 ]. Kundu et al [ 60 ] demonstrated that eugenol presented antioxidant proprieties and could promote a vasorelaxant effect, and a calcium blockade in high concentrations. The protective effect was observed in arteries that were exposed to heavy metal (As and Hg).…”

“…Additionally, dose-dependent EOAR blunted the phenylephrine-induced contraction of the aortic rings. Isolated LO reduced the hypercontraction of aortic segments induced by heavy metals, such as As and Hg, and involved the enhancement of NO synthesis and the blockade of voltage-dependent calcium channels [ 60 ]. Deep investigation of the mechanism of action of LO indicated further participation of soluble guanylyl cyclase and K + channel on its vasorelaxant effects [ 73 ].…”

IOP Lowering Effects of Ocimum basilicum Seed Extract in Two Rabbit Models of Ocular Hypertension

“…Hence it is likely that OBE reduces IOP by inhibiting cholinesterase activity. Additionally, linalool is known to cause direct vasorelaxation [24,25]. Since trabecular meshwork cells are known to possess smooth muscle cells like properties [26], it is likely that OBE causes relaxation of trabecular meshwork resulting in enhanced aqueous humor drainage and consequently reduced IOP.…”

Effects of Terpenes and Terpenoids of Natural Occurrence in Essential Oils on Vascular Smooth Muscle and on Systemic Blood Pressure: Pharmacological Studies and Perspective of Therapeutic Use

“…The direct relaxing effect of LN on VSM has been suggested to be responsible for the hypotensive effect of this compound. In the aorta of normotensive rats with endothelium, LN (100 μM) had a relaxing effect on PHE-induced contraction [27,29].…”