Effect of mersalyl on the thick ascending limb of Henle's loop

Abstract

The cortical portion of the thick ascending limb of Henle's loop was dissected from rabbit kidneys and perfused in vitro. There was active chloride transport resulting in net sodium chloride reabsorption from the tubule lumen, with the electrical potential difference (PD) oriented positive in the lumen. The addition of mersalyl (≥ 10-5M) to the lumen caused the PD and net Cl flux to decrease, indicating inhibition of the active Cl transport. The decrease in PD caused by the drug in the lumen was approximately 50% at concentrations equal to or greater than 10-5M, and the decrease in Cl transport (measured at 3 x 10-5M) was similar in magnitude. Addition of p chloromercuribenzoate to the tubule lumen immediately reversed the effect of mersalyl administration. The diuresis caused by mercurials in vivo similarly is reversed by p chloromercuribenzoate administration. Therefore, the effect of mersalyl on the isolated perfused thick ascending limbs of Henle's loop in vitro can be identified with its diuretic effect in vivo. Mersalyl in the bath was inactive except at a higher concentration (10-4M) and the effect was not reversible. It is concluded that the diuretic effect of mercurials is due, at least in part, to inhibition by these drugs in the tubule lumen of active Cl transport in the thick ascending limb of Henle's loop.