Pharmacologic probing of mercuric chloride-induced renal dysfunction in the neonatal rat

Acetazolamide, furosemide, chlorothiazide and amiloride are pharmacologic agents that act primarily in the proximal tubule, loop of Henle, early distal tubule and late distal tubule and collecting duct, respectively. These diuretic agents were used to evaluate the functional integrity of discrete segments of the nephron in the neonatal rat following treatment with a known nephrotoxicant. Six-day old rats were treated s.c. with the proximal tubule toxicant mercuric chloride (1 or 3.2 mg/kg) or saline. Twenty-four hours later, when evidence of mercury nephrotoxicity is detectable, creatinine clearance and the fractional excretion of water and various components of the filtrate were determined using a 2-hr clearance period immediately after injection of a diuretic. The effects of mercury (3.2 mg/kg) were consistent with its ability to cause acute renal failure and proximal tubular necrosis and also indicated an apparent disruption of the cycling of urea in the nephron. A decrease in the fractional excretion of water, combined sodium and potassium and total osmotic solutes indicated that the diuretic response to acetazolamide was markedly attenuated in the mercuric chloride-treated pups whereas the responses to furosemide, chlorothiazide and amiloride were not altered by mercury treatment. Results from this study illustrate the specificity of these diuretics as pharmacologic probes of mercuric chloride induced renal dysfunction and, therefore, support their usefulness as tools in the investigation of renal developmental toxicity.