Effect of lead on renal responsiveness to antidiuretic hormone in young rats

Abstract

The effect of lead exposure on antidiuretic hormone (ADH) action in young rats was investigated. Without administration of exogenous ADH, urine volume was greater and urine osmolality values were lower in the lead-exposed rats compared to pair-fed controls during 24 hr of water deprivation. Exogenous ADH administration to lead-exposed rats during 24 hr of water deprivation reduced urine volume and elevated urine osmolality to values similar to those obtained from control animals. Plasma ADH concentrations from lead-exposed rats were as high if not higher than those from control animals. Dose-response studies indicated that in lead-exposed animals urine flow rate was reduced less by each dose of ADH than that observed in the control animals. These results suggest that renal lead toxicity impairs ADH action on the renal tubule contributing to the polyuria observed in lead-exposed rats. There was no difference in the in vitro basal or vasopressin-stimulated renal medullary adenylate cyclase activity between control and lead-exposed rats suggesting the mechanism of the lead effect on ADH action may not be related to adenylate cyclase activity. However, results from dose-response studies on the effect of lead on renal medullary adenylate cyclase activity suggest that the similarity between control and lead-treated rats is due to an artifact of the procedure for measurement of enzyme activity. The addition of ethylene bis(oxyethylenenitrilo) tetraacetic acid (EGTA) to the reaction medium may have obscured the inhibitory effects of lead on adenylate cyclase activity.