Nitric oxide in unilateral ureteral obstruction: effect on regional renal blood flow.
BACKGROUND
Ureteral obstruction (UO) is characterized by reduced blood flow and loss of tissue mass in the involved kidney(s). Vasoactive mediators interact to produce an initial hyperemia, followed by a sustained decrease in renal blood flow in the obstructed kidney. Nitric oxide (NO) has been shown to play a central role in the acute hyperemic response to UO. Its role in the reduced perfusion of prolonged UO is less studied.


METHODS
Ureteral obstruction was achieved by ligation of the distal left ureter and maintained for 24 hours. Blood flow was studied in untreated animals and after the administration of the NO synthase (NOS) inhibitor N-mono-methyl L-arginine and the NO donor sodium nitroprusside. Tissue was collected for localization and quantitation of NOS. Serum and renal tissue L-arginine levels were measured in control and UO settings.


RESULTS
Blood flow in the obstructed kidney diminished to approximately 50% of control values after 24 hours of UO. NOS blockade led to a further decrease in blood flow. Supplementation with exogenous nitrates restored renal blood flow to levels approaching control values. Serum and tissue L-arginine levels did not change with UO. NOS expression was seen to increase with increasing duration of obstruction, with staining most pronounced in the renal tubules.


CONCLUSIONS
NO plays a vasodilatory role even in the hypoperfusion of prolonged UO. The administration of exogenous nitrates has a restorative effect on blood flow, suggesting therapeutic potential in UO.
Hegarty
N J
NJ
Department of Surgery, Mater Misericordiae Hospital and University College Dublin, Dublin, Ireland.
Young
L S
LS
Kirwan
C N
CN
O'Neill
A J
AJ
Bouchier-Hayes
D M
DM
Sweeney
P
P
Watson
R W
RW
Fitzpatrick
J M
JM
D000818:Animals; D001120:Arginine / Q000097:blood / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007684:Kidney Tubules / Q000201:enzymology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D014517:Ureteral Obstruction / Q000503:physiopathology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat