Effect of Heavy Metals on Sodium Transport in Vitro

Abstract

Heavy metal salts have been extensively used to study the pathophysiology of acute renal failure. There have been numerous studies which have carefully characterized the alterations in renal functions, renal hemodynamics, and vasoactive substances in heavy metal-induced acute renal failure. Based on these studies (Flamenbaum et al., 1974), it was proposed that activation of a tubuloglomerular feedback mechanism may be an important mediator for the initiation of acute renal failure. In this proposal it is assumed that heavy metal salts (uranyl nitrate or mercuric chloride) initially interact with epithelial cells of the renal tubule so as to reduce fluid and electrolyte transport primarily in early nephron segments. As a consequence of the altered transport function in the early segments, the composition of the fluid delivered to the distal nephron and macula densa is changed. The changed fluid composition results in increased renin release and thereby activation of tubuloglomerular feedback (Schnermann et al., 1970). This latter step results in the observed decrease in glomerular filtration rate and changes in renal hemodynamics. The renal hemodynamic changes in turn will tend to augment and perpetuate the initial tubular dysfunction so that the usually negative feedback mechanisms for tubuloglomerular feedback do not become operative.