A REEVALUATION OF THE DETERMINANTS OF GLOMERULAR-FILTRATION RATE

Several factors are potentially able to change the glomerular filtrati on rate (GFR) and thereby participate in its regulation, but only a fe w factors seem to be physiologically important. The variable nature of proximal tubular pressure should be recognized as important in the re gulation of GFR. It is argued that a distinction should be made betwee n the terms 'autoregulation of GFR' and 'regulation of GFR'. The tubul oglomerular feedback mechanism (TGF) is an important factor for autore gulatory control of GFR. When perturbations result in major increases in tubular flow, the TGF saturates. Proximal tubular pressure then inc reases and becomes the major factor responsible for the stabilization of GFR. Changes in the proximal reabsorption rate (APR) are important for long-term variations in GFR (regulation of GFR). Small changes in the APR cause near parallel changes in the GFR mainly through the TGF mechanism, while larger changes in the APR cause near parallel changes in the GFR mainly because of the effect on tubular pressure. The hydr aulic resistance in the distal nephron segments is an additional facto r in regulating GFR, through its effect on proximal tubular pressure. The stimulus to the TGF mechanism also depresses renin release. The re sulting local angiotensin II concentration has effects both on the art eriolar resistances and on the APR. The renin-angiotensin system and T GF are therefore considered to be integrated parts of a common control system regulating GFR. According to the hypothesis advocated here, TG F-mediated changes in afferent arteriolar resistance and angiotensin-m ediated changes in efferent arteriolar resistance and APR cooperate in counteracting perturbations in proximal tubular pressure and Henle lo op flow. However, because of the biphasic proximal effect of angiotens in II, a major unresolved question is whether physiological increases in endogenous local angiotensin II concentrations stimulate or inhibit proximal reabsorption.