Eukaliuric diuresis and natriuresis in response to the K-ATP channel blocker U37883A: Micropuncture studies on the tubular site of action

1 Systemic application of U37883A, a blocker of ATP sensitive potassium (K- ATP) channels, elicits diuresis and natriuresis without significantly alter ing urinary potassium excretion. 2 To elucidate tubular sites of action upstream to the distal nephron, micr opuncture experiments were performed in nephrons with superficial glomeruli of anaesthetized Munich-Wistar-Fromter rats during systemic application of U37883A (1, 5 or 15 mg kg(-1) i.v.). 3 The observed eukaliuric diuresis and natriuresis in response to U37883A a t 15 mg kg(-1) was accompanied by an increase in early distal tubular flow rate (V-ED) from 10-18 nl min(-1) reflecting a reduction in fractional reab sorption of fluid up to this site (FR-fluid) of 13%. The latter proposed an effect on water-permeable segments such as the proximal tubule which could fully account for the observed reduction in fractional reabsorption of Na up to the early distal tubule (FR-Na+) of 8% and the increase in early dis tal tubular Na+ concentration ([Na+](ED)) from 35-51 mM whereas [K+](ED) wa s left unaltered. 4 In comparison, furosemide (3 mg kg(-1) i.v.), which acts in the water-imp ermeable thick ascending limb, elicited diuresis, natriuresis and kaliuresi s which were associated with a fall in FR-Na+ of 10% with no change in FR-f luid, and a rise in [Na+](ED) from 42-117 mM and [K+](ED) from 1.2-5.7 mM w ith no change in VED 5 Direct late proximal tubular fluid collections confirmed a significant in hibition of fluid reabsorption in proximal convoluted tubule in response to systemic application of U37883A. 6 These findings suggest that the diuretic and natriuretic effect upstream to the distal tubule in response to systemic application of U37883A involve s actions on water-permeable segments such as the proximal convoluted tubul e.