INTRATUBULAR APPLICATION OF SODIUM-AZIDE INHIBITS LOOP OF HENLE REABSORPTION AND TUBULOGLOMERULAR FEEDBACK RESPONSE IN ANESTHETIZED RATS

Sodium azide (NaN3, AZ) is a potent inhibitor and uncoupler of oxidati ve phosphorylation as well as a nitrovasodilator after being converted to nitric oxide (NO). We studied the effect of intratubular applicati on of AZ on loop of Henle reabsorption and tubuloglomerular feedback ( TGF) employing renal micropuncture experiments in nephrons with superf icial glomeruli of anesthetized Munich-Wistar-Fromter rats. During per fusion of Henle's loop downstream from an obstructing wax block, AZ (3 x10(-5) mol/l and 3x10(-4) mol/l) concentration-dependently increased early distal tubular flow rate and sodium and potassium ion concentrat ion (V-ED, [Na+](ED), [K+](ED)). In comparison, application of furosem ide (10(-4) mol/l), the action of which is restricted to the water-imp ermeable thick ascending limb of Henle's loop (TALH) and the macula de nsa, similarly increased [Na+](ED) and [K+](ED), but did not affect V- ED. The effect of AZ on loop of Henle reabsorption appeared to be pred ominantly localized upstream to the TALH since (1) AZ significantly in hibited net fluid reabsorption (the latter being completely abolished at 3x10-4 mol/l), (2) the effect of AZ on [Na+](ED) and [K+](ED) could be mimicked by perfusing the Henle's loop at a flow rate that caused a comparable increase in V-ED (reflecting a comparable load to TALH), and (3) the effects of AZ and furosemide were additive. In spite of th e increase in [Na+](ED) and [K+](ED), intratubular application of AZ c aused a concentration-dependent inhibition of TGF response, the latter being assessed as the fall in early proximal tubular stop flow pressu re during perfusion of Henle's loop at increasing flow rate. Like AZ a nd furosemide, the NO donor sodium nitro prusside (10(-4) mol/l) blunt ed the TGF response, but in contrast to furosemide or AZ, it caused a minor decrease in VED, without changing [Na+](ED) or [K+](ED). The inh ibitory effect of AZ on TGF was abolished by the NO scavenger carboxy PTIO. In summary, AZ inhibits both reabsorption in the water-permeable segment of Henle's loop and the TGF response. The effect on reabsorpt ion may be linked to metabolic inhibition rather than NO release, wher eas the blunted TGF response appears to involve conversion to NO.