Effects of mercury on the isolated perfused rat tail vascular bed are endothelium-dependent

The effects of mercury on vascular smooth muscle results in vasoconstriction, but the mechanism of this action is not elucidated yet. To investigate this issue we examined the effects of HgCl2 in the isolated rat tail vascular bed. The tail artery was dissected, cannulated, and perfused at a constant flow (2.5 ml/min) with Krebs solution plus EDTA 0.03 mM at 36°C. After equilibration for 30 min the effects of increasing concentrations of HgCl2 (0.5, 1, 2, 5, and 10 μM) on the perfusion pressure were investigated. Concentrations of HgCl2, 2 μM and above, significantly increased perfusion pressure. Blockade of α receptors (prazosin 84 ng/ml) did not alter the responses to HgCl2, suggesting that the metal does not induce the release of neurotransmitters from sympathetic nerve terminals. To investigate the possible role of endothelium on the vasoconstriction produced by HgCl2, preparations were pre-contracted with 10-7 M phenylephrine or perfused with 5 μM HgCl2 for 20 min. Acetylcholine-vasodilated preparations precontracted with phenylephrine demonstrating the integrity of the endothelial nitric oxide-releasing mechanism. In contrast, after perfusion with 5 μM HgCl2, the vasodilation produced by acetylcholine was abolished. In the presence of either phenylephrine or HgCl2 the effects of sodium nitroprusside remained unchanged. Pretreatment with 30 μM indomethacin fully prevented the HgCl2-induced vasoconstriction. However, the endothelium- dependent vasodilation in response to acetylcholine was significantly reduced after indomethacin plus HgCl2 treatment, meanwhile the vasodilation produced by nitroprusside remained unchanged. Pretreatment with L-arginine (1 mM) did not prevent the vasoconstriction induced by HgCl2, nor did it restore the ability of acetylcholine to produce vasodilation, and it did not alter the response to sodium nitroprusside. The possibility of HgCl2's actions mediated by the formation of free radicals was also investigated. The administration of 10 mM histidine significantly reduced the vasoconstrictor response if used before HgCl2 treatment without improving the reduced vasodilation produced by acetylcholine. These results are consistent with the hypothesis that the vasoconstriction produced by HgCl2 may be mediated by the formation of superoxide anions, stimulating the production of a COX- derived vasoconstrictor agent and by reducing the endothelial vasodilator activity.