L-NAME, a nitric oxide synthase inhibitor, diminishes oxidative damage in urinary bladder partial outlet obstruction.
Partial bladder outlet obstruction (PBOO) results in cellular damage due to ischemia and reperfusion injury. Our study seeks to establish how early this damage can occur and the role that nitric oxide may play in its pathophysiology. Surgical PBOO (1, 3, and 7 days) were performed on male New Zealand White rabbits. Half of the animals were premedicated for 3 days with N(G)-nitro-l-arginine methyl ester(l-NAME), an inhibitor of nitric oxide synthase before obstruction. Bladder weight increased with duration of PBOO but was significantly lower at 3 and 7 days in animals treated with l-NAME compared with their untreated counterparts. Contractile function decreased progressively with PBOO duration. At 1 day postobstruction, bladder contractility was significantly lower in the l-NAME rabbits than in the untreated rabbits. At 3 and 7 days, contractility of the l-NAME bladders was equal or higher than the untreated bladders. The level of hypoxia at 1 day after obstruction was significantly higher in the l-NAME-treated animals than in the untreated controls but equal at 3 and 7 days obstruction. Increased nitrotyrosine was seen by Western blot in all obstructed animals. However, the amount was significantly less in the l-NAME-treated animals at 3 and especially at 7 days. Nerve density decreased progressively after obstruction; however, it decreased to a significantly lesser degree in the l-NAME-treated bladders than in the untreated groups. These results suggest that l-NAME pretreatment enhanced ischemic damage at 1 day after obstruction but protected the bladder from nitric oxide-generated free radical damage at the later time periods by inhibiting the generation of nitrotyrosine.
Conners
William
W
Basic and Pharmaceutical Sciences, Albany College of Pharmacy, 106 New Scotland Ave., Albany, NY 12208, USA.
Whitebeck
Catherine
C
Chicester
Paul
P
Legget
Robert
R
Lin
Alpha Dian-Yu
AD
Johnson
Arnold
A
Kogan
Barry
B
Levin
Robert
R
Mannikarottu
Anita
A
D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009929:Organ Size; D011470:Prostatic Hyperplasia / Q000209:etiology; D011817:Rabbits; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D001743:Urinary Bladder / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D001748:Urinary Bladder Neck Obstruction / Q000378:metabolism* / Q000503:physiopathology
C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester