Decreased expression of brain nitric oxide synthase in macula densa cells and glomerular epithelial cells of rats with mercury chloride-induced acute renal failure.

To elucidate the mechanisms responsible for the development of HgCl(2)-induced acute renal failure (ARF), we examined the expression of brain type (b) nitric oxide synthase (NOS), which is involved in the generation of the vasodilator nitric oxide (NO), in the renal cortex of rats at 20 h after exposure to 7.5 mg/kg HgCl(2). Both blood urea nitrogen and serum creatinine were significantly increased in rats exposed to HgCl(2) relative to control rats, indicating the induction of ARF resulting from HgCl(2) exposure. Histopathological analysis demonstrated that, in addition to necrosis of proximal tubule epithelial cells, necrosis of macula densa cells and swelling of glomerular epithelial cells were observed in the renal cortex of rats with HgCl(2)-induced ARF. Consequently, the number of pars maculata segments was decreased by 42% in rats with HgCl(2)-induced ARF compared to control rats. The primary sites of bNOS mRNA and protein expression were macula densa cells and glomerular epithelial cells in the renal cortex of control rats and rats with HgCl(2)-induced ARF. The abundance of the bNOS mRNA and protein was significantly decreased in rats with HgCl(2)-induced ARF relative to control rats. These observations suggest that the production of the vasodilator NO derived from bNOS is decreased at the glomerulus level in the HgCl(2)-induced ARF setting. Thus, the reduction in bNOS expression may in part contribute to the progression of HgCl(2)-induced ARF through the deterioration of glomerular hemodynamics. In addition, the decrease in bNOS expression may be primarily the result of cell injury caused by the cytotoxic effect of HgCl(2).