Effect of furosemide administration on glomerular and tubular dynamics in the rat

Furosemide, a potent diuretic, has also been shown (1) to inhibit or reduce tubuloglomerular feedback activity, (2) act as a vasodilatory agent, and (3) exhibit a modest carbonic anhydrase inhibitory effect, which could potentially reduce proximal tubule reabsorption. If furosemide can inhibit tubuloglomerular feedback as well as cause vasodilation, then glomerular filtration rate (GFR) should increase through alterations in the dynamics of glomerular ultrafiltration. The effect of acute furosemide infusion (4 mg/kg of body wt per hour) on glomerular and tubular dynamics was examined in Munich-Wistar rats by two protocols: The first allowed a 3% volume depletion (based on body wt) to occur as a result of furosemide administration (group 1); the second allowed a complete replacement of volume after furosemide administration (group 2). The results demonstrated that when volume status was maintained after furosemide administration, the nephron filtration rate remained constant (35 +/- 3 vs. 33 +/- 2 nl/min, NS) despite a twofold increase in distal flow rate (5 +/- 1 vs. 10 +/- 1 nl/min, P less than 0.01), indicating an inhibition or suppression of the tubuloglomerular feedback system. With either protocol, furosemide administration did not alter total nephron vascular resistance and nephron blood flow (190 +/- 17 vs. 200 +/- 15 ml/min); however, the afferent arteriolar resistance did decrease in rats in which volume status was maintained. Finally, with volume status maintained, we were not able to demonstrate a reduction in absolute proximal fluid reabsorption despite a 7 mm Hg increase in interstitial hydrostatic pressure (4 +/- 1 to 11 +/- 1 mm Hg, P less than 0.01) and no compensatory increase in interstitial oncotic pressure. These data indicate that tubuloglomerular feedback was inhibited but that GFR was not increased. Major changes occurred in interstitial pressures and interstitial volume after furosemide administration, but absolute proximal reabsorption remained constant.