Inhibition of nitric oxide synthase enhances superoxide activity in canine kidney.
To evaluate the role of a potential interaction between superoxide anion (O(2)(-)) and nitric oxide (NO) in regulating kidney function, we examined the renal responses to intra-arterial infusion of a superoxide dismutase mimetic, tempol (0.5 mg.kg(-1).min(-1)), in anesthetized dogs treated with or without NO synthase inhibitor, N(omega)-nitro-l-arginine (NLA; 50 microg.kg(-1).min(-1)). In one group of dogs (n = 10), tempol infusion alone for 30 min before NLA infusion did not cause any significant changes in renal blood flow (RBF; 5.2 +/- 0.4 to 5.0 +/- 0.4 ml.min(-1).g(-1)), glomerular filtration rate (GFR; 0.79 +/- 0.04 to 0.77 +/- 0.04 ml.min(-1).g(-1)), urine flow (V; 13.6 +/- 2.1 to 13.9 +/- 2.5 microl.min(-1).g(-1)), or sodium excretion (U(Na)V; 2.4 +/- 0.3 to 2.2 +/- 0.3 micromol.min(-1).g(-1)). Interestingly, when tempol was infused in another group of dogs (n = 12) pretreated with NLA, it caused increases in V (4.4 +/- 0.4 to 9.7 +/- 1.4 microl.min(-1).g(-1)) and in U(Na)V (0.7 +/- 0.1 to 1.3 +/- 0.2 micromol.min(-1).g(-1)) without affecting RBF or GFR. Although NO inhibition caused usual qualitative responses in both groups of dogs, the antidiuretic (47 +/- 5 vs. 26 +/- 4%) and antinatriuretic (67 +/- 4 vs. 45 +/- 11%) responses to NLA were seen much less in dogs pretreated with tempol. NLA infusion alone increased urinary excretion of 8-isoprostane (13.9 +/- 2.7 to 22.8 +/- 3.6 pg.min(-1).g(-1); n = 7), which returned to the control levels (11.6 +/- 3.4 pg.min(-1).g(-1)) during coadministration of tempol. These data suggest that NO synthase inhibition causes enhancement of endogenous O(2)(-) levels and support the hypothesis that NO plays a protective role against the actions of O(2)(-) in the kidney.
Majid
Dewan S A
DS
Dept. of Physiology, SL 39, Tulane Univ. Health Sciences Center, 1430 Tulane Ave., New Orleans, LA 70112, USA. majid@tulane.edu
Nishiyama
Akira
A
Jackson
Keith E
KE
Castillo
Alexander
A
D000818:Animals; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D028421:Isoprostanes / Q000652:urine; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000652:urine; D019335:Nitroarginine / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D028421:Isoprostanes; D009566:Nitrates; D009573:Nitrites; D013113:Spin Labels; D013481:Superoxides; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; C001803:tempol