Low Mercury Concentration Produces Vasoconstriction, Decreases Nitric Oxide Bioavailability and Increases Oxidative Stress in Rat Conductance Artery

Abstract

Mercury is an environmental pollutant that reduces nitric oxide (NO) bioavailability and increases oxidative stress, having a close link with cardiovascular diseases, as carotid atherosclerosis, myocardial infarction, coronary heart disease and hypertension. One of the main sites affected by oxidative stress, which develops atherosclerosis, is the aorta. Under acute exposure to low mercury concentrations reactive oxygen species (ROS) production were only reported for resistance vessels but if low concentrations of mercury also affect conductance arteries it is still unclear. We investigated the acute effects of 6 nM HgCl2 on endothelial function of aortic rings measuring the reactivity to phenylephrine in rings incubated, or not, with HgCl2 for 45 min, the protein expression for cyclooxygenase 2 (COX-2) and the AT1 receptor. HgCl2 increased Rmax and pD2 to phenylephrine without changing the vasorelaxation induced by acetylcholine and sodium nitroprusside. Endothelial damage abolished the increased reactivity to phenylephrine. The increase of Rmax and pD2 produced by L-NAME was smaller in the presence of HgCl2. Enalapril, losartan, indomethacin, furegrelate, the selective COX-2 inhibitor NS 398, superoxide dismutase and the NADPH oxidase inhibitor apocynin reverted HgCl2 effects on the reactivity to phenylephrine, COX-2 protein expression was increased, and AT1 expression reduced. At low concentration, below the reference values, HgCl2 increased vasoconstrictor activity by reducing NO bioavailability due to increased ROS production by NADPH oxidase activity. Results suggest that this is due to local release of angiotensin II and prostanoid vasoconstrictors. Results also suggest that acute low concentration mercury exposure, occurring time to time could induce vascular injury due to endothelial oxidative stress and contributing to increase peripheral resistance, being a high risk factor for public health.

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

“…As the optimal response was seen at 6.0 nM, further studies were performed at 6 nM to ensure healthy tissue and linearity in contractile response. Similar concentration ranges for Hg(II) have been shown to be effective by other workers (7). In the absence of agonist, arsenic 25 µM or mercury (6 nM) incubation did not lead to any significant tension change from the applied passive tension of 2.0 g.…”

“…This was reset to the passive tension of 2.0 g before eliciting contraction by PE. SNP caused relaxation has also been reported by other investigators (7). …”

“…The concentration of HgCl 2 that is toxic for humans is about 1.5 µg/L of blood i.e. 7 nM (7). Unlike other studies where the effect of Hg(II) was seen on pre-contracted aortic segments, in this study we have compared the maximum contractile response of aortic segments that have been pre-incubated with As(III) and Hg(II) in the relevant concentration range (5).…”

“…At low and high mercury concentrations in pre-contracted aorta, relaxation and hypercontraction, respectively, has been reported (5). Oxidative stress and endothelial dysfunction are consistently observed in arsenic and mercury exposed aortic smooth muscle, but emerging evidence suggests that these factors also have a causal role in calcium influx leading to vasoconstriction (6, 7). Reactive oxygen species (ROS) may directly alter vascular function or cause changes in vascular tone by altering nitric oxide (NO) bioavailability or signalling (8).…”

Treatment with high dose of atorvastatin reduces vascular injury in diabetic rats

“…The increase of ROS in DM may result from reduced activity of antioxidant enzymes, such as superoxide dismutase (SOD) [9] and catalase [10], and an increase in NADPH oxidase activity [6,11,12]. Therefore, the increase in oxidative stress observed in DM may lead to a reduction in NO bioavailability and accelerate atherosclerosis in conductance vessels [13].…”