RESUMEN
Mercury is an environmental pollutant and a threat to human health. Mercuric chloride (HgCl2)-induced acute renal failure has been described by several reports, but the mechanisms of renal dysfunction remain elusive. This study tested the hypothesis that HgCl2 directly impairs renal vascular reactivity. Additionally, due to the mercury toxicity on the proximal tubule, we investigated whether the HgCl2-induced natriuresis is accompanied by inhibition of Na+/H+ exchanger isoform-3 (NHE3). We found that 90-min HgCl2 infusion (6.5 µg/kg i.v.) remarkably increased urinary output, reduced GFR and renal blood flow, and increased vascular resistance in rats. "In vitro" experiments of HgCl2 infusion in isolated renal vascular bed demonstrated an elevation of perfusion pressure in a concentration- and time-dependent manner, associated with changes on the endothelium-dependent vasodilatation and the flow-pressure relationship. Moreover, by employing "in vivo" stationary microperfusion of the proximal tubule, we found that HgCl2 inhibits NHE3 activity and increases the phosphorylation of NHE3 at serine 552 in the renal cortex, in line with the HgCl2-induced diuresis. Changes in renal proximal tubular function induced by HgCl2 were parallel to increased urinary markers of proximal tubular injury. Besides, atomic spectrometry showed that mercury accumulated in the renal cortex. We conclude that acute HgCl2 exposure causes renal vasoconstriction that is associated with reduced endothelial vasodilator agonist- and flow-mediated responses and inhibition of NHE3-mediated sodium reabsorption. Thus, our data suggest that HgCl2-induced acute renal failure may be attributable at least in part by its direct effects on renal hemodynamics and NHE3 activity.
