Interaction of O 2 − and NO in the Thick Ascending Limb

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Abstract
Abstract— Nitric oxide (NO) is an important regulator of NaCl absorption by the thick ascending limb of the loop of Henle (THAL). The free radical superoxide (O 2 − ) reacts with NO, decreasing its bioavailability. O 2 − is produced by mitochondria and various oxidases, some of which are present in the THAL. However, the ability of the THAL to produce O 2 − and its interaction with NO have not been studied. We hypothesized that NO bioavailability is decreased by O 2 − . THALs were isolated and perfused and NO production was measured with an NO-selective microelectrode. Addition of L-Arg (250 μmol/L), but not D-arginine, to the bath increased NO release by 34.8±11.8 pA (n=7). The response to L-Arg was completely abolished by the NO synthase inhibitor L-NAME (n=7). Scavenging THAL O 2 − with the superoxide dismutase (SOD) mimetic Tempol (50 μmol/L) increased L-Arg-induced NO release. At all concentrations of L-Arg tested (50, 100, 250, 500, and 750 μmol/L), further addition of Tempol to the bath significantly increased NO release by THALs. Addition of SOD (300 U/mL) to the bath increased L-Arg-induced NO levels by 82% (n=5; P P − absorption by 35%. Subsequent addition of Tempol (50 μmol/L) to the bath further decreased Cl − absorption by 35% (n=6; P 2 − . In addition, we believe our studies are the first to show that endogenous O 2 − may act as a physiological regulator of nephron NaCl transport.

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