Effects ofl-arginine andl-NAME on chronic partial bladder outlet obstruction in rabbit

Abstract

(NO) is synthesized from L-arginine by nitric oxide synthase (NOS). NOS can be inhibited by N G -nitro-L-arginine methyl ester (L-NAME) and stimulated by supplementing the diet with L-arginine. The aim of this study was to investigate the influence of NOS activity on the response of rabbits to chronic partial bladder outlet obstruction (PBOO). Surgical PBOOs (2 and 8 wk) were performed on male New Zealand White rabbits. Before obstruction, one-third of the animals were premedicated for 7 days with L-NAME and another third with L-arginine. The results are summarized as follows. First, bladder weight after 8-wk PBOO was significantly lower in animals treated with L-arginine compared with both untreated and rabbits treated with L-NAME. Second, contractile function decreased progressively with PBOO duration. However, after 8 wk of PBOO, the L-arginine group had significantly greater contractile function compared with the notreatment group, and the L-NAME group had significantly lower contractile function compared with the no-treatment group. Third, at 8 wk following PBOO, the level of protein oxidation and nitration was lowest for the L-arginine group and highest in the L-NAME group. These studies clearly demonstrated that increasing blood flow by stimulating NOS significantly protected the bladder from PBOO dysfunctions, whereas inhibiting blood flow by L-NAME enhanced the dysfunctions mediated by PBOO. contractility; angiogenesis; nitric oxide NITRIC OXIDE (NO), a neurotransmitter responsible for relaxation activity in the lower urinary tract and corpus cavernosum, is synthesized from L-arginine in a reaction catalyzed by NO synthase (NOS) (6). NO is also known to be a powerful and ubiquitous regulator of vascular tone, and thus in several systems is shown to regulate blood flow. In cardiac studies, impaired release of NO may be an important factor in the development of ischemia-reperfusion (I/R) injury. Conversely, it has been demonstrated that administration of NO donors or L-arginine reduces infarct size and improves the postischemic recovery of cardiac performance and endothelial function in animal models of myocardial ischemia and reperfusion (28,36,37). Similarly, other studies have shown that exogenously administered L-arginine decreases oxidative stress in the liver and brain (9) and that an increase in NO formation has a beneficial effect on the progression of cellular and molecular parameters of tubulointerstitial fibrosis caused by obstruction of the ureter (27). With regards to bladder function, our previous study demonstrated that feeding rabbits a diet high in L-arginine was beneficial for both control rabbits and those with 2 wk of severe partial bladder outlet obstruction (PBOO) (38).Contradicting the protective effects, NO is reported to generate free radicals in I/R injury, which has been shown in other studies to be one of the primary causes of progression of bladder dysfunction (3). It has been demonstrated that NO-related damage due to nitrotyrosine was elevated with PBOO (23). Pretreatment wi...

Effects of nitric oxide inhibitors in mice with bladder outlet obstruction

“…Moreover, although early administration of L-NAME enhances ischemic damage at the beginning of the obstructive process, it inhibits the generation of nitrotyrosine and results in preservation of nerve density, reducing initial free radical damage associated with BOO (5). On the other hand, at chronic obstruction, L-NAME also prevents increases in blood flow and ROS generation from the compromised mitochondria, but nitrotyrosine production enhances and leads to worsen in bladder function (24). …”

Melatonin and 1400 W Ameliorate both Intestinal and Remote Organ Injury Following Mesenteric Ischemia/Reperfusion

“…As to the ameliorative effects of 1400W, there are conflicting data supporting both a beneficial and a harmful effect of NO on I/R injury [49]. NO is one of the most important mediators in pathophysiological changes of tissues.…”

“…NO and ONOO -are eventually converted to nitrite (NO 2 ) and/or nitrate (NO 3 ), i.e., NO x . In addition, ONOO -nitrates several proteins to form 3-NT which is an indicator of ONOO - [49]. Therefore, NO x and/or 3-NT levels are used as an indirect but reliable indicator for NO and ONOOÀ formation in vivo, respectively [35].…”

Comparison of the Efficacy of Melatonin and 1400W on Renal Ischemia/Reperfusion Injury: A Role for Inhibiting iNOS

“…[22,33] Regarding the ameliorative effects of 1400W, there are conflicting data for both a beneficial and a harmful effect of NO on I/R injury. [38] NO is one of the most important mediators in pathophysiological changes of tissues. Under physiologic conditions, NO maintains vascular tone and inhibits aggregation and adhesion of neutrophils and platelets to vascular endothelium; these are beneficial aspects of NO function.…”