Postglomerular vascular protein concentration: evidence for a causal role in governing fluid reabsorption and glomerulotubular balance by the renal proximal tubule

Barry M. Brenner; Julia L. Troy

doi:10.1172/JCI106501

We tested the relationship between postglomerular microvascular protein concentration and rates of sodium and water transfer by rat proximal tubules. Using recently described microperfusion techniques, efferent arterioles and branch peritubular capillaries of normal hydropenic rats were perfused with colloid-free Ringer's solution, and isoncotic (9.0-10.0 g/100 ml) and hyperoncotic (15 g/100 ml) albumin-Ringer's solutions. Reabsorption in adjacent proximal tubules was studied using free-flow techniques, with initial collections obtained during normal blood perfusion, recollections during experimental microperfusion, and in some tubules, repeat recollections after microperfusion and spontaneous resumption of blood perfusion. Colloid-free perfusion resulted in a uniform inhibition of proximal reabsorption (absolute and fractional). Despite identical techniques, substitution of isoncotic and hyperoncotic perfusates resulted, on average, in unchanged and increased rates of reabsorption, respectively. These findings of direct linear changes in reabsorption in response to changes in postglomerular protein concentrations usually occurred in the absence of significant changes in filtered load, and were nearly always found to be reversible within minutes of cessation of experimental perfusion.

Given this evidence of a causal relationship between postglomerular oncotic pressure and proximal reabsorption, we undertook to determine whether this relationship is responsible for the parallel adjustments in proximal reabsorption that follow changes in GFR (glomerulotubular balance). Using a separate group of hydropenic rats, proximal reabsorption was studied, initially during partial aortic constriction (during which renal perfusion pressure, single nephron GFR, absolute proximal reabsorption, and calculated filtration fraction all were reduced below levels prior to constriction), and again while adjacent efferent arteriolar and peritubular capillary protein concentrations, but not GFR, were restored to normal (preconstriction) levels by microperfusion with 9-10 g/100 ml albumin-Ringer's solution. During this dissociation of GFR and postglomerular protein concentration, absolute and fractional proximal reabsorption nearly always increased in parallel with the changes in the latter, thereby demonstrating that glomerulotubular balance is mediated, at least in part, by changes in postglomerular oncotic pressure brought about by changes in filtration fraction.