Intrinsic nitric oxide and superoxide production regulates descending vasa recta contraction

Cao C, Edwards A, Sendeski M, Lee-Kwon W, Cui L, Cai C, Patzak A, Pallone TL. Intrinsic nitric oxide and superoxide production regulates descending vasa recta contraction. Am J Physiol Renal Physiol 299: F1056-F1064, 2010. First published August 11, 2010; doi:10.1152/ajprenal.00070.2010.-Descending vasa recta (DVR) are 12- to 15-mu m microvessels that supply the renal medulla with blood flow. We examined the ability of intrinsic nitric oxide (NO) and reactive oxygen species (ROS) generation to regulate their vasoactivity. Nitric oxide synthase (NOS) inhibition with N(omega)-nitro-L-arginine methyl ester (L-NAME; 100 mu mol/l), or asymmetric N(G),N(G)-dimethyl-L-arginine (ADMA; 100 mu mol/l), constricted isolated microperfused DVR by 48.82 +/- 4.34 and 27.91 +/- 2.91%, respectively. Restoring NO with sodium nitroprusside (SNP; 1 mmol/l) or application of 8-Br-cGMP (100 mu mol/l) reversed DVR vasoconstriction by L-NAME. The superoxide dismutase mimetic Tempol (1 mmol/l) and the NAD(P)H inhibitor apocynin (100, 1,000 mu mol/l) also blunted ADMA-or L-NAME-induced vasoconstriction, implicating a role for concomitant generation of ROS. A role for ROS generation was also supported by an L-NAME-associated rise in oxidation of dihydroethidium that was prevented by Tempol or apocynin. To test whether H(2)O(2) might play a role, we examined its direct effects. From 1 to 100 mu mol/l, H(2)O(2) contracted DVR whereas at 1 mmol/l it was vasodilatory. The H(2)O(2) scavenger polyethylene glycol-catalase reversed H(2)O(2) (10 mu mol/l)-induced vasoconstriction; however, it did not affect L-NAME-induced contraction. Finally, the previously known rise in DVR permeability to (22)Na and [(3)H]raffinose that occurs with luminal perfusion was not prevented by NOS blockade. We conclude that intrinsic production of NO and ROS can modulate DVR vasoactivity and that L-NAME-induced vasoconstriction occurs, in part, by modulating superoxide concentration and not through H(2)O(2) generation. Intrinsic NO production does not affect DVR permeability to hydrophilic solutes.