Effects of chlorpropamide on loop of Henle function and plasma renin

We have suggested that inhibition of renin release by sodium chloride is related to increased absorptive solute transport in the loop of Henle. In the rat, we have shown that reduced chloride transport in the loop is associated with increased renin release. Based on indirect evidence, it has been suggested that chlorpropamide (CPMD) increases loop solute transport. This study directly evaluates the effect of CPMD on loop chloride transport and plasma renin activity (PRA) in the male Sprague-Dawley rat. Loop of Henle chloride reabsorption (measured by recollection micropuncture) and PRA were determined before and after acute infusion of CPMD (N = 8) or vehicle (N = 8). Although delivery to the loop was not significantly changed, CPMD increased (P less than 0.05) absolute loop chloride reabsorption from 1798 pEq/min +/- 200 SE to 2453 pEq/min +/- 206 SE. PRA was decreased (P less than 0.01) from 9.2 ng/ml/hr +/- 1.0 SE to 5.6 ng/ml/hr +/- 0.8 SE following CPMD infusion. Comparable vehicle infusion did not alter loop chloride reabsorption or PRA. Arterial pressure, and whole kidney and single nephron glomerular filtration rates were unchanged following infusion of CPMD or vehicle. These results demonstrate that an increase in loop chloride reabsorption is associated with a decrease in renin release. This observation is consistent with the hypothesis that renin release is inversely related to the magnitude of chloride transport in the thick ascending limb of the loop of Henle.