<scp>l</scp>-NAME, a nitric oxide synthase inhibitor, diminishes oxidative damage in urinary bladder partial outlet obstruction

Conners, William; Whitebeck, Catherine; Chicester, Paul; Legget, Robert E.; Lin, Alpha Dian-Yu; Johnson, A.; Kogan, Barry A.; Levin, Robert M.; Mannikarottu, Anita

doi:10.1152/ajprenal.00261.2005

Cited by 52 publications

(49 citation statements)

References 22 publications

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“…L-NAME has been shown in other studies of bladder function to enhance ischemia damage at 1 day after PBOO but protected the bladder from nitric oxide-generated free radical damage at the later time periods [12]. This is different to what we found in this study.…”

Section: Discussioncontrasting

confidence: 99%

The immediate effect of nitric oxide on the rabbit bladder after ovariectomy

Juan¹,

Mannikarottu²,

Schuler³

et al. 2008

Nitric Oxide

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Ovariectomy resulted in decreased blood flow and hypoxia to the bladder mucosa and smooth muscle. Nitric oxide (NO) played an important role in regulating bladder function during bladder ischemia and reperfusion. This study was designed to evaluate the role of NO on bladder function in the first few days after ovariectomy. Female rabbits were separated into three groups, one which received no medication, pre-medicated with N(omega) -nitro-L-arginine methyl ester (L-NAME) and the third treated with L-arginine. Non-ovariectomized controls and at 1 and 3 days post-ovariectomy, animals from each group were euthanized. Cystometry and in vitro isometric contractile responses were recorded and the oxidative stress markers, nitrotyrosine and protein carbonylation were determined. L-NAME treatment did not significantly alter bladder function after ovariectomy. L-arginine fed, ovariectomized rabbits had lower intravesical pressure and better contractile responses to all forms of stimulation than the ovariectomized rabbits with or without L-NAME. Furthermore, the ovariectomized ones with or without L-NAME had higher oxidative stress markers than L-arginine fed rabbits. This study clearly demonstrates that feeding rabbits with L-arginine can protect the bladder from oxidative free radical damage following short term ovariectomy.

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Section: Discussioncontrasting

confidence: 99%

The immediate effect of nitric oxide on the rabbit bladder after ovariectomy

Juan¹,

Mannikarottu²,

Schuler³

et al. 2008

Nitric Oxide

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“…It has been demonstrated that NO-related damage due to nitrotyrosine was elevated with PBOO (23). Pretreatment with N G -nitro-L-arginine methyl ester (L-NAME), which acts as a competitive inhibitor of NOS, significantly inhibited the generation of nitrotyrosine (8). Also, reports by Saito et al (30 -32) showed that treatment with L-NAME can reduce apoptosis induced by I/R in the bladder and significantly increase the contractile responses compared with the I/R group without L-NAME.…”

mentioning

confidence: 99%

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

Lin

Levin²,

Chichester³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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(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...

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“…This observation confirms previous findings that in animal models and in patients suffering from bladder outflow obstruction, there is damage to the autonomic innervation (Sibley, 1987;Williams et al, 1993;Brading, 1997;Levin et al, 2000;de Jongh et al, 2009). Oxidative stress due to ischemia followed by reperfusion, has been demonstrated in obstructed bladders and may underlie the changes in muscle function and patchy denervation of the detrusor (Conners et al, 2006;de Jongh et al, 2009;Scheepe et al, 2011). There was no inhibition of bethanechol-induced responses (up to 10 -5 -M) in obstructed guinea pig bladders compared to shams or controls.…”

Section: Efs and Effect Of Cholinergic Agonists In Obstructionmentioning

confidence: 86%

“…The mechanism responsible for increased residual volume and bladder capacity in obstruction is still unclear. Oxidative damage to the autonomic innervation and to the detrusor muscle, demonstrated in animal models of bladder obstruction (Conners et al, 2006;de Jongh et al, 2009;Scheepe et al, 2011) could be involved. It has been recently shown that distension-sensitive bladder afferents had higher threshold volumes and lower tension sensitivity in obstructed rats (Zeng et al, 2012).…”

Section: Other Factors Influenced Obstruction-induced Bladder Overactmentioning

confidence: 99%

Conscious voiding during bladder obstruction in guinea pigs correlates with contractile activity of isolated bladders

Nicholas

Keightley

Brookes

et al. 2015

Autonomic Neuroscience

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Purpose: There are many hypotheses accounting for detrusor overactivity, however the exact mechanisms are still incompletely understood. We used a model of bladder outlet obstruction in male guinea pigs as a way to produce detrusor overactivity. The objective was to determine whether changes in voiding of obstructed guinea pigs correlates with specific changes in contractile activity of their isolated bladders in vitro. Material and methods: Conscious voiding activity of sham-operated and obstructed animals was measured in metabolic cages. Contractile activity (spontaneous or evoked by distension, electrical field stimulation or cholinergic agonists) was recorded via a pressure transducer in the isolated bladders in vitro. Results: The frequency of conscious voiding increased (while voiding volume decreased) in the obstructed group, compared with the sham-operated group, 4 weeks after surgical intervention. In comparison to the sham-operated animals, the bladders from the obstructed guinea pigs were enlarged and inflamed, their frequency of spontaneous contractions was higher, while the amplitudes of electrical field stimulation (EFS)-induced contractions and bladder compliance were lower. Changes in conscious voiding during obstruction were significantly associated with alterations in structural parameters (bladder weight, thickness and histological damage score) and functional contractile parameters (frequency of spontaneous contractions, amplitude of EFS-induced contractions and bladder compliance) of their isolated bladders. Conclusions: Our findings revealed significant association between conscious voiding and structural and contractile activity changes of the isolated bladders in obstruction. The data suggest that change in contractile activity of the bladder itself is a major contributor to obstruction-induced bladder overactivity.

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l-NAME, a nitric oxide synthase inhibitor, diminishes oxidative damage in urinary bladder partial outlet obstruction

Cited by 52 publications

References 22 publications

The immediate effect of nitric oxide on the rabbit bladder after ovariectomy

The immediate effect of nitric oxide on the rabbit bladder after ovariectomy

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

Conscious voiding during bladder obstruction in guinea pigs correlates with contractile activity of isolated bladders

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