Peritubular fluid viscosity modulates H+ flux in proximal tubules through NO release

Abstract

We evaluated the effects of increasing the viscosity (η) in peritubular capillary perfusates (PCP; 20 mM HNaPO4 −-Ringer, pH 7.4) on proximal convoluted tubule (PCT) acidification. Micropuncture experiments were performed with simultaneous luminal and peritubular perfusion. Changes in pH of a 20 mM HNaPO4 −-Ringer (pH 7.4 at t = 0) droplet placed in PCT lumen were measured with H+-sensitive microelectrodes. By adding neutral dextran (molecular wt 300,000–400,000) to the PCP, η was increased. The effect of 10−5 M ATP added to normal-η PCP was evaluated. High η increased H+ flux (85 and 97% when η was increased 20 and 30%, respectively, above the control value). This increase was abolished by adding the nitric oxide antagonist N ω-nitro-l-arginine (l-NNA; 10−4 M) or the purinoreceptor antagonists suramin (10−4 M) and reactive blue 2 (3 × 10−5 M). Addition of 5 × 10−3 Ml-arginine to the peritubular perfusate overcame the inhibitory effect of l-NNA on high-η-induced increase in H+ flux. ATP increased H+ flux (80%), and this effect was blocked by l-NNA. These results suggest that changes in η can modulate proximal H+ flux, at least in part, through ATP-dependent nitric oxide release from the endothelial cells of the peritubular capillaries.