THE NATRIURETIC ACTIVITY OF THE K-37883A DISPLAYS AN ADH-DEPENDENCE( CHANNEL BLOCKER U)

We reported previously that K+ channel blockers induce diuresis and na triuresis in conscious and anesthetized rats. Free-water clearance stu dies suggested that K+ channel blockers inhibit NaCl reabsorption in t he thick ascending limb (TAL) by blocking K+ recycling through a low-c onductance, usually open, apical ATP-sensitive K+ channel. In the pres ent study, we measured the effect of U-37883A (15 mg/kg, i.v.) on Nareabsorption in rats preconditioned to alter ADH levels. In water-load ed animals with suppressed ADH levels, U-37883A was 50% less natriuret ic than in saline-loaded rats. Infusion of ADH to water-loaded rats re stored the natriuretic response to a level comparable to saline-loaded rats. Loss of natriuretic efficacy was for secondary to changes in GF R or renal perfusion pressure since GFRs did not vary before or after drug administration in any of the respective groups. Decreases in bloo d pressure were not significantly different in saline-loaded, water-lo aded and water-loaded/ADH rats. The natriuretic response of U-37883A a s varied by ADH levels may be the first observation, in vivo, to suppo rt the observation that the cotransporter in TAL can exist in two mode s as previously observed in vitro by Hebert and colleagues. (C) 1998 P ious Science. All rights reserved.