The efferent limb of the tubuloglomerular feedback system

Abstract

The effector mechanisms which constitute the efferent limb of the tubuloglomerular feedback system were examined after the administration of benzolamide, a carbonic anhydrase inhibitor, which decreased proximal tubule fluid reabsorption by approximately 8 nl/min and transiently increased delivery of fluid out of the proximal tubule. Since benzolamide administration resulted in a decrease in nephron filtration rate (SNGFR) from 29.2 to 21.1 nl/min, late proximal flow rate returned to control values. If the proximal tubule was blocked after benzolamide by insertion of an oil block, the SGNFR returned towards control values. If a proximal tubule oil block was inserted prior to control measurements, SNGFR did not decrease. These data suggest that benzolamide reduces SNGFR by activating tubulo-glomerular feedback mechanisms secondary to increases in the rate of distal delivery. Analysis of the determinants of glomerular ultrafiltration before and after benzolamide administration revealed that the decrease in SNGFR was solely the result of a decrease in nephron plasma flow secondary to increases in afferent and efferent glomerular arteriolar resistance. No change in either the hydrostatic pressure gradient (delta P) or the glomerular permeability coefficient (LpA) was observed. Continuous infusion in saralasin, an angiotensin II antagonist, prevented the reduction in SNGFR and nephron plasma flow after benzolamide. These studies suggest that changes in nephron plasma flow are involved in a mediating the tubuloglomerular feedback response and that angiotensin II may have a role in the effector mechanism.