Altered Nitric Oxide Synthase, Arginase and Ornithine Decarboxylase Activities, and Polyamine Synthesis in Response to Ischemia of the Rabbit Detrusor

Kawano, Keizo; Masuda, Hitoshi; Yano, Masataka; Kihara, Kazunori; Sugimoto, Akihiro; Azuma, Hiroshi

doi:10.1016/s0022-5347(06)00515-5

Cited by 16 publications

(17 citation statements)

References 20 publications

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“…In the rat, intravesical administration of NO depressed bladder hyperactivity induced by chemical irritants (20)(21)(22)(23)(24)(25). After damage to the urinary bladder, NO generation is most likely caused by i-NOS, which in other tissues is up regulated by inflammatory stimuli and the activity of which is independent of calcium concentration (13).…”

Section: Discussionmentioning

confidence: 99%

Activity and Expression of Nitric Oxide Synthase in Rat Bladder after Sacral Neuromodulation

Minardi

Ghiselli

Mocchegiani

et al. 2008

Int J Immunopathol Pharmacol

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The aim of our study is to investigate the effects of chronic sacral neuromodulation on Nitric Oxide (NO) metabolism in the rat bladder. 26 female Sprangue-Dawley rats were considered: group I, normal control rats; group II, a sham treatment, in whom catheters for electrical stimulation were placed in the SI foramen bilaterally and left in place for 21 days, without performing neuromodulation; group III in whom electrical sacral neuromodulationwas performed for 21 days. Finally a cystectomy was performed and the bladder biopsy specimens were sent for immunostaining with n-NOS and i-NOS. Morphological and immunohistochemical analysis was carried out, and evaluated in urothelial cells, endothelial cells and muscle fibers of the muscularis propria. Differences between the 3 groups were analyzed by Student Newman-Keuls test. We. could observe that urothelial and endothelial i-NOS (37.00±4.69 and 59.00±7.42 respectively) and urothelial n-NOS (36.80±7.85) expression are significantly increased in neuromodulated rats, compared to groups 1 and 2 (p < 0.005). In conclusion, the increase of i-NOS expression on endothelial cells after sacral neuromodulation could be in some way related to angiogenetic responses in the microvascular structures; the increase of n-NOS and i-NOS expression on urothelial cells can suggest that NO is able to influence the plasticity of bladder response, inducing the release of messengers within the urothelium. This study can therefore improve our understanding of the mechanisms of sacral neuromodulation on chronic bladder dysfunction; further studies will need to better demonstrate the role of angiogenesis in the bladder after sacral neuromodulation and to investigate the effects of neuromodulation in rats with chronically induced bladder dysfunction.Sacral neuromodulation for treating chronic functional voiding dysfunction has become established in Urology; but although it represents a valid treatment option for patients who do not show improvement with conventional pharmacological and surgical treatment, very little is known regarding the underlying mechanism of electrical stimulation (1-2): some authors found that the blockade of C-

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Section: Discussionmentioning

confidence: 99%

Activity and Expression of Nitric Oxide Synthase in Rat Bladder after Sacral Neuromodulation

Minardi

Ghiselli

Mocchegiani

et al. 2008

Int J Immunopathol Pharmacol

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“…Arginase is a 105‐kD homotrimeric enzyme that requires manganese for the hydrolysis of L‐arginine to form L‐ornithine and urea. Because L‐arginine is the substrate of both arginase and NOS, arginase activity can effectively inhibit NO‐dependent processes by depleting the substrate pool available for NO biosynthesis, for example, as observed in the cellular immune response and the regulation of smooth muscle tone 41–43 . Accordingly, arginase inhibition can effectively enhance NO‐dependent physiological processes by enhancing L‐arginine bioavailability to NOS 44–47 .…”

Section: Modulation Mechanisms Of No (Fig 2)mentioning

confidence: 99%

Significance of Nitric Oxide and its Modulation Mechanisms in Micturition Disorders

Masuda

Yano

Ichiyanagi

et al. 2009

LUTS

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Nitric oxide (NO) pathway is of critical importance in the physiological regulation of micturition reflex. NO released from urothelium and suburothelium depresses afferent micturition pathway, while in the central nervous system NO has dual effects on afferent pathway; i.e, excitatory effect in the spinal cord and brain stem and inhibitory effect in the forebrain. Elevated endogenous NO synthase (NOS) inhibitors and increased arginase activity in the lower urinary tracts contribute to NO deficiency, leading to impairement of NO‐mediated relaxations and excitation of different pathway. Therefore, manipulation of endogenous NOS inhibitors and arginase may be new targets of micturition disorders.

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“…Arginase also has an important role in providing l ‐ornithine for the synthesis of polyamines controlling cell proliferation and differentiation. Ornithine decarboxylase (ODC) is the rate limiting enzyme for the conversion of l ‐ornithine to putrescine, which is further converted to spermidine by spermidine synthase 8 …”

Section: Role Of Arginasementioning

confidence: 99%

“…Also, we reported that, in the early events of ischemic bladder, arginase may have two independent roles, that is (i) the activation of arginase/ODC/polyamine pathways in the muscle injury and remodeling following ischemia; and (ii) the endogenous negative regulation of NO production by limiting the l ‐arginine substrate for NOS 8 …”

Section: Role Of Arginasementioning

confidence: 99%

“…A second major pathway of arginine metabolism is via arginase, which catalyzes the conversion of l ‐arginine to ornithine plus urea. Since l ‐arginine is the substrate of both arginase and NOS, arginase activity can effectively inhibit the NO‐dependent process by depleting the substrate pool available for NO biosynthesis, for example, as observed in the cellular immune response and the regulation of smooth muscle tone 6–8 . Accordingly, arginase inhibition can effectively enhance the NO‐dependent physiological process by enhancing l ‐arginine bioavailability to NOS 9–12 .…”

Section: Introductionmentioning

confidence: 99%

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Significance of nitric oxide and its modulation mechanisms by endogenous nitric oxide synthase inhibitors and arginase in the micturition disorders and erectile dysfunction

Masuda

2008

Int J of Urology

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Evidence indicates that nitric oxide (NO) deficiency contributes to micturition disorders, especially in the afferent pathway and erectile dysfunction (ED). Two possible causes of NO deficiency are substrate (L-arginine) limitation and increased levels of endogenous inhibitors of NO synthase (particularly asymmetric dimethylarginine: ADMA) in plasma and tissues. Elevated tissues of ADMA and N G -monomethyl-Larginine (L-NMMA) have been reported to be associated with impaired NO-mediated urethral, trigonal and cavernosal relaxations by pelvic ischemia. Also, plasma ADMA may help to identify underlying cardiovascular disease in men with ED. Decreased L-arginine availability to NO synthase is due to the shunting of L-arginine into other pathways such as arginase. Interaction between NO synthase and arginase has been reported to be involved in NO-mediated urethral and prostatic relaxations. Also, increased arginase activity in cavernosal tissues likely contributes to the ED that accompanies diabetes mellitus and aging. Therefore, arginase inhibition has been reported to enhance the NO-dependent physiological process for erectile function.

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Altered Nitric Oxide Synthase, Arginase and Ornithine Decarboxylase Activities, and Polyamine Synthesis in Response to Ischemia of the Rabbit Detrusor

Cited by 16 publications

References 20 publications

Activity and Expression of Nitric Oxide Synthase in Rat Bladder after Sacral Neuromodulation

Activity and Expression of Nitric Oxide Synthase in Rat Bladder after Sacral Neuromodulation

Significance of Nitric Oxide and its Modulation Mechanisms in Micturition Disorders

Significance of nitric oxide and its modulation mechanisms by endogenous nitric oxide synthase inhibitors and arginase in the micturition disorders and erectile dysfunction

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