Our laboratory has previously shown that mice lacking neuronal nitric oxide synthase (nNOS) are defective in fluid absorption ( J v) and HCO[Formula: see text]absorption ( J HCO3) in the proximal tubule and develop metabolic acidosis. The present study examined the transport of fluid and HCO[Formula: see text] 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). [3H]inulin and total CO2 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 · min−1 · 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 · 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 · min−1 · mm−1) and J v (1.56 ± 0.17 vs. 1.55 ± 0.16 nl · min−1 · mm−1) did not change significantly in eNOS knockout mice. These results indicated that iNOS upregulates Na+ and HCO[Formula: see text]transport, whereas eNOS does not directly modulate Na+ and HCO[Formula: see text] transport in the kidney proximal tubules.
Absence of salt sensitivity in iNOS knockout mice
