Persistence of EDHF pathway and impairment of the nitric oxide pathway after chronic mercury chloride exposure in rats: Mechanisms of endothelial dysfunction

Abstract

<jats:p> Chronic mercury exposure impairs vascular function, leading to the depression of endothelium-dependent vasodilatation. Loss of the nitric oxide (NO) pathway has been implicated, but little is known about effects on other endothelial mediators. This study investigated the mechanisms of endothelial dysfunction in rats subjected to chronic mercury chloride exposure. The endothelium-dependent relaxation of rat aorta evoked by acetylcholine (ACh) and isoproterenol was impaired in a dose-dependent manner by chronic mercury chloride exposure. Endothelium-independent responses to sodium nitroprusside (SNP) were not affected by chronic mercury chloride exposure. In healthy vessels, ACh-induced relaxation was inhibited by L-N-nitroarginine methyl ester (L-NAME; 10<jats:sup>–4</jats:sup>M) and partially by glybenclamide (10<jats:sup>–5</jats:sup>M), indicating the involvement of NO and endothelium-derived hyperpolarizing factor (EDHF). In vessels from mercury-exposed rats, responses to ACh were insensitive to L-NAME but were significantly reduced by glybenclamide, indicating selective loss of NO-mediated relaxation. In vessels from mercury-exposed rats, responses to ACh were partially restored after treatment with the antioxidant, superoxide dismutase (SOD) and catalase, this effect was not seen when aorta from exposed group was incubated with L-NAME along with SOD and catalase indicating selective loss of NO-mediated vasodilatation and with no affect the EDHF-mediated component of relaxation. The results imply that chronic mercury exposure selectively impairs the NO pathway as a consequence of oxidative stress, while EDHF is able to maintain endothelium-dependent relaxation at a reduced level. </jats:p>

Modulation of Vasodilator Response via the Nitric Oxide Pathway after Acute Methyl Mercury Chloride Exposure in Rats

“…Mercury has been recognized as a risk factor for cardiovascular disease [1–3, 9]. Mercury is reported to significantly increase systolic and diastolic blood pressure [19, 20].…”

“…The role of mercury toxicity as a possible risk factor in cardiovascular disease has been discussed, and reports on the toxic effects of metals in several diseases among humans including the vascular diseases have been well documented [1–4]. The loss of endothelial function is one of the most commonly observed vascular effects of mercury exposure [5–9]. As has been widely reported, this endothelial dysfunction leads to a loss of endothelium-dependent vasorelaxation.…”

“…As has been widely reported, this endothelial dysfunction leads to a loss of endothelium-dependent vasorelaxation. This loss at least in part is due to the reduction in NO bioavailability because of increased ROS production [8, 9]. Previous studies from our group have demonstrated that chronic mercury exposure selectively impairs the NO pathway as a consequence of oxidative stress, while endothelium-dependent hyperpolarizing factor (EDHF) is able to maintain endothelium-dependent relaxation at a reduced level [9].…”

“…This loss at least in part is due to the reduction in NO bioavailability because of increased ROS production [8, 9]. Previous studies from our group have demonstrated that chronic mercury exposure selectively impairs the NO pathway as a consequence of oxidative stress, while endothelium-dependent hyperpolarizing factor (EDHF) is able to maintain endothelium-dependent relaxation at a reduced level [9]. Though an increase in NO was observed in our previous study, it failed to attain significance as reductions in NO bioavailability may be due to the increased ROS production, which was responsible for the endothelial dysfunction [10, 11].…”

Mercury Exposure and Endothelial Dysfunction

“…[6][7][8][9][10] Oxidative stress that results in endothelial dysfunction and loss of endothelium-dependent vasorelaxation is one of the most commonly observed cardiovascular effects of mercury exposure. [11][12][13][14] The aim of this review is to explore the relationship between mercury exposure, CVD, and endothelial cell (EC) function/ dysfunction, focusing predominantly on interaction/balance between bioavailability of nitric oxide (NO) and oxidative stress.…”