Role of iNOS and eNOS in modulating proximal tubule transport and acid-base balance.
Our laboratory has previously shown that mice lacking neuronal nitric oxide synthase (nNOS) are defective in fluid absorption (J(v)) and HCO absorption (J(HCO3)) in the proximal tubule and develop metabolic acidosis. The present study examined the transport of fluid and HCO in the proximal tubule and acid-base status in mice lacking two other isoforms of NOS, inducible NOS (iNOS) and endothelial NOS (eNOS). Proximal tubules were microperfused in situ in wild-type and NOS knockout mice by methods previously described (Wang T, Yang C-L, Abbiati T, Schultheis PJ, Shull GE, Giebisch G, and Aronson PS. Am J Physiol Renal Physiol 277: F298-F302, 1999). [(3)H]inulin and total CO(2) concentrations were measured in the perfusate and collected fluid, and net J(v) and J(HCO3) were analyzed. These data show that J(HCO3) was 35% lower (71.7 +/- 6.4 vs. 109.9 +/- 7.3 pmol x min(-1) x mm(-1), n = 13, P < 0.01) and J(v) was 38% lower (0.95 +/- 0.15 vs. 1.54 +/- 0.17 nl. min(-1) x mm(-1), n = 13, P < 0.05) in iNOS knockout mice compared with their wild-type controls. Addition of the iNOS-selective inhibitor L-N(6)-(1-iminoethyl) lysine, reduced both J(v) and J(HCO3) significantly in wild-type, but not in iNOS knockout, mice. In contrast, both J(HCO3) (93.3 +/- 7.9 vs. 110.6 +/- 6.18 pmol x min(-1) x mm(-1)) and J(v) (1.56 +/- 0.17 vs. 1.55 +/- 0.16 nl. min(-1) x mm(-1)) did not change significantly in eNOS knockout mice. These results indicated that iNOS upregulates Na(+) and HCO transport, whereas eNOS does not directly modulate Na(+) and HCO transport in the kidney proximal tubules.
Wang
Tong
T
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. tong.wang@yale.edu
D000042:Absorption; D000136:Acid-Base Equilibrium / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004573:Electrolytes / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III
D001639:Bicarbonates; D004573:Electrolytes; D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse