Direct analysis of the effector mechanism of the tubuloglomerular feedback system

Abstract

The determinants of single nephron glomerular filtration rate (SNGFR) were examined in Munich-Wistar rats by direct glomerular micropuncture during orthograde perfusion of the same nephron''s loop of Henle with isotonic Ringer solution at 0 and 40 nl/min. At the higher loop flow rate, SNGFR decreased significantly by .apprx. 35% relative to the nonperfused condition. Whereas indirect stop-flow estimates of mean glomerular capillary hydraulic pressure (.hivin.PGC) also decreased significantly by .apprx. 8 mm Hg, directly measured .hivin.PGC values were unaffected by the change in loop flow rate. Both glomerular plasma flow rate (QA) and the ultrafiltration coefficient decreased significantly at the higher loop flow rate, thereby accounting for the measured reduction in SNGFR. Given the observed near constancy of directly measured .hivin.PGC and significant reduction in QA, both afferent and efferent arteriolar resistances were calculated to increase in response to the higher loop perfusion rate. In a separate set of experiments, cessation of glomerular filtration increased directly measured .hivin.PGC in the condition of zero loop perfusion but not when the loop was perfused at a high flow rate. Apparently, tubuloglomerular feedback-induced changes in SNGFR are not accompanied by changes in .hivin.PGC, and tubuloglomerular feedback regulation of GFR is mediated by alterations in vasomotor tone of preglomerular, glomerular and postglomerular microvessels. Based on the close anatomical contact between mesangial cells and these vessels, a single effector mechanism channeled through mesangial contractility is suggested.