Eukaliuric diuresis and natriuresis in response to the KATP 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 altering urinary potassium excretion. 2 To elucidate tubular sites of action upstream to the distal nephron, micropuncture 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 at 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 reabsorption 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 distal tubular Na+ concentration ([Na+](ED)) from 35-51 mM whereas [K+](ED) was left unaltered. 4 In comparison, furosemide (3 mg kg(-1) i.v.), which acts in the water-impermeable thick ascending limb, elicited diuresis, natriuresis and kaliuresis which were associated with a fall in FR-Na+ of 10% with no change in FR-fluid, and a rise in [Na+](ED) from 42-117 mM and [K+](ED) from 1.2-5.7 mM with no change in VED 5 Direct late proximal tubular fluid collections confirmed a significant inhibition 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 involves actions on water-permeable segments such as the proximal convoluted tubule.