Inhibition of nitric oxide synthase does not influence urinary nitrite plus nitrate excretion after renal ischemic injury.
OBJECTIVE
Whether renal nitric oxide production caused by ischemia/reperfusion (I/R) influences the urinary excretion of nitric oxide (NO) metabolites (nitrite and nitrate) is far from being elucidated. In the present study, we evaluated the role of NO synthase inhibition using N(G)-nitro- L-arginine methyl ester ( L-NAME) in a model of experimental renal I/R injury.


METHODS
Male Wistar rats were used in our experiments, and renal I/R injury was achieved after a 30-min occlusion of the bilateral renal artery followed by a 60-min period of reperfusion. Renal function including nitrite plus nitrate excretion and hemodynamics in reperfused kidneys were measured in the presence and absence of L-NAME.


RESULTS
Intravenous application of L-NAME (5 mg/kg body weight) resulted in a marked reduction of urine flow, renal plasma flow (0.7 +/- 0.3 ml/min), and the glomerular filtration rate (0.1 +/- 0.01 ml/min), but a significant increase in NO excretion (FENOx, 67.9 +/- 10.5%). In addition we found after L-NAME injection a significant increase of the fractional excretion of sodium (FENa, 49.3 +/- 7.7%) and lithium (FELi, 70.2 +/- 1.6%), as well as the renal vascular resistance compared with animals with renal I/R but non-treated with L-NAME ( P<0.001). Furthermore, we observed a high correlation between FENOx and FELi (r(2)=0.80, P<0.01).


CONCLUSIONS
Our results suggest that renal excretion of NO derivatives is not influenced by NO production during renal I/R injury, although NO contributes to the tubular transport capacity in the ischemia/reperfused kidney.
Ogawa
Toshihisa
T
Department of General Surgery, University of Ulm, Steinhövelstrasse 9, 89075 Ulm, Germany.
Nussler
Andreas K
AK
Tuzuner
Eda
E
Mimura
Yoshikazu
Y
Kaminishi
Michio
M
Beger
Hans G
HG
D000818:Animals; D004195:Disease Models, Animal; D007511:Ischemia / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009566:Nitrates / Q000652:urine*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D009573:Nitrites / Q000652:urine*; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D015427:Reperfusion Injury / Q000378:metabolism*; D013997:Time Factors
D009566:Nitrates; D009573:Nitrites; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester