A re-evaluation of the determinants of glomerular filtration rate

Several factors are potentially able to change the glomerular filtration rate (GFR) and thereby participate in its regulation, but only a few factors seem to be physiologically important. The variable nature of proximal tubular pressure should be recognized as important in the regulation of GFR. It is argued that a distinction should be made between the terms 'autoregulation of GFR' and 'regulation of GFR'. The tubuloglomerular feedback mechanism (TGF) is an important factor for autoregulatory control of GFR. When perturbations result in major increases in tubular flow, the TGF saturates. Proximal tubular pressure then increases 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 hydraulic resistance in the distal nephron segments is an additional factor in regulating GFR, through its effect on proximal tubular pressure. The stimulus to the TGF mechanism also depresses renin release. The resulting local angiotensin II concentration has effects both on the arteriolar resistances and on the APR. The renin-angiotensin system and TGF are therefore considered to be integrated parts of a common control system regulating GFR. According to the hypothesis advocated here, TGF-mediated changes in afferent arteriolar resistance and angiotensin-mediated changes in efferent arteriolar resistance and APR cooperate in counteracting perturbations in proximal tubular pressure and Henle loop flow. However, because of the biphasic proximal effect of angiotensin II, a major unresolved question is whether physiological increases in endogenous local angiotensin II concentrations stimulate or inhibit proximal reabsorption.