Vasorelaxant effects of mercury on rat thoracic aorta

Abstract

<jats:p> Mercury, a heavy metal, is widespread and persistent in the environment and has been elucidated as a possible risk factor in cardiovascular diseases. Mercury has been reported to selectively impair the nitric oxide (NO) pathway in the vascular endothelium as a consequence of oxidative stress. Conversely, mercury per se causes endothelium-dependent vasorelaxation at lower concentration via the NO pathway. Little is known about the effects of mercury per se on other endothelial mediators. To elucidate possible mechanisms involved in this action, isometric tension was measured in aortic rings precontracted with phenylephrine (10 µM) from Wistar rats. Responses to increasing concentrations of inorganic mercuric chloride (10<jats:sup>−12</jats:sup>–10<jats:sup>−5</jats:sup> M) were obtained in the presence and absence of endothelium. Inorganic mercury produced a biphasic response in endothelium-intact aortic rings and produced only vasoconstriction in endothelium-denuded aortic rings. To study the possible underlying mechanisms for the biphasic response of mercury, increasing concentrations of mercuric chloride (10<jats:sup>−12</jats:sup>–10<jats:sup>−5</jats:sup> M) were used before and after N<jats:sup>G</jats:sup>-nitro-l-arginine methyl ester (L-NAME (10<jats:sup>−4</jats:sup> M)), glybenclamide (10<jats:sup>−5</jats:sup> M), superoxide dismutase (10 U/ml) + catalase (100 U/ml), and nifedipine (10<jats:sup>−4</jats:sup> M) treatment. Results suggest that mercury produces endothelium-dependent relaxation at low concentration mediated by endothelial-generated NO and endothelium-derived hyperpolarizing factor and endothelium-independent contraction resulting from the blockade of l-type Ca<jats:sup>2+</jats:sup> channels by generation of free radicals. </jats:p>

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

“…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). Optimum incubation time was found to be 40 min.…”

“…Mercury has also been reported to enhance contraction responses in aortic segments (7). A biphasic effect of mercury has recently been reported, with vasorelaxation at lower concentrations and vasoconstriction at higher concentrations in pre-contracted aortic segments (5). We did not observe biphasic responses in this study, possibly because we measured the tension after 40 min of Hg(II) incubation of the resting aortic segments which may lead to generation of ROS.…”

“…Cardiovascular effects of arsenic and mercury toxicity include hypertension, atherosclerosis, peripheral vascular disorders and vasoconstriction (2, 3, 4). 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).…”

Impaired participation of potassium channels and Na+/K+‐ATPase in vasodilatation due to reduced nitric oxide bioavailability in rats exposed to mercury

“…Wiggers et al used lower doses of mercury and showed a reduction in the participation of potassium channels in mesenteric resistance arteries. However, other authors have demonstrated that acute incubation with different concentrations of mercury can stimulate or suppress potassium efflux currents that are sensitive to TEA or glibenclamide in human B lymphocytes, proximal tubular cells of the frog kidney and rat thoracic aorta . Because endothelial NO can directly activate the potassium channels, especially BK Ca , and ROS can negatively modulate the activity of these channels, we evaluated the vasodilatation in response to the NO donor SNP after a pre‐incubation with tiron to test the response to a known amount NO without the influence of local ROS.…”

Mercury Exposure and Endothelial Dysfunction

“…Similar observations were reported by our group ascertaining that mercury exposure produces a biphasic response-vasorelaxation at lower concentrations and vasoconstriction at higher concentrations. 73 The ECs secrete oxygen-derived free radicals and H 2 O 2 in response to stress. 74 Superoxide anion inactivates NO, 69 resulting in vasoconstriction of arteries.…”