Peritubular fluid viscosity modulates H+ flux in proximal tubules through NO release.
We evaluated the effects of increasing the viscosity (eta) 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, eta was increased. The effect of 10(-5) M ATP added to normal-eta PCP was evaluated. High eta increased H+ flux (85 and 97% when eta was increased 20 and 30%, respectively, above the control value). This increase was abolished by adding the nitric oxide antagonist N(omega)-nitro-L-arginine (L-NNA; 10(-4) M) or the purinoreceptor antagonists suramin (10(-4) M) and reactive blue 2 (3 x 10(-5) M). Addition of 5 x 10(-3) M L-arginine to the peritubular perfusate overcame the inhibitory effect of L-NNA on high-eta-induced increase in H+ flux. ATP increased H+ flux (80%), and this effect was blocked by L-NNA. These results suggest that changes in eta can modulate proximal H+ flux, at least in part, through ATP-dependent nitric oxide release from the endothelial cells of the peritubular capillaries.
Díaz-Sylvester
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Instituto de Investigaciones Cardiológicas-Consejo Nacional de Investigaciones Científicas y Técnicas, 1122 Buenos Aires, Argentina.
Mac Laughlin
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Amorena
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D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D003911:Dextrans / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011522:Protons; D051381:Rats; D017208:Rats, Wistar; D011983:Receptors, Purinergic / Q000187:drug effects / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology; D014783:Viscosity
D000970:Antineoplastic Agents; D003911:Dextrans; D004791:Enzyme Inhibitors; D011522:Protons; D011983:Receptors, Purinergic; D009569:Nitric Oxide; D013498:Suramin; D000255:Adenosine Triphosphate; D006152:Cyclic GMP