Long‐term nitric oxide deficiency causes muscarinic supersensitivity and reduces β<sub>3</sub>‐adrenoceptor‐mediated relaxation, causing rat detrusor overactivity

Mónica, Fabíola Z.; Bricola, Alice; Báu, Fernando R.; Freitas, Leandro Luiz Lopes de; Teixeira, Simone Aparecida; Muscará, Marcelo Nícolas; Abdalla, Fernando Maurício Francis; Porto, Catarina S.; Nucci, Gilberto De; Zanesco, Angelina; Antunes, Edson

doi:10.1038/bjp.2008.39

Cited by 46 publications

(43 citation statements)

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“…These results suggest that NO has an inhibitory effect in muscular relaxation both in the bladder and in the urethra of animals with chronic deficiency of NO. As demonstrated in a previous experimental study, the systemic reduction of NO causes detrusor overactivity with a decrease in the functional relaxation of the urethra (4,6). Chronic L-NAME treatment also increased the number of micturition cycles in comparison with control animals.…”

Section: Discussionsupporting

confidence: 66%

“…And the amount of cGMP results from the balance between production (NO) and degradation made by phosphodiesterase are enzymes that can hydrolyze and inactivate cyclic nucleotides. It is known that NO is involved in relaxation of the detrusor, bladder neck, urethra and prostate (6,12).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the inhibition of arginases, which degrade L-arginine into L--ornithine, decreased neurogenic DO in chronic spinal cord-injured (SCI) rats (5). Recently, it was also showed that 4-week treatment with the NOS blocker L-NAME causes in vitro detrusor smooth muscle (DSM) supersensitivity to muscarinic agonists via increased levels of [H 3 ]-inositol-phophate, accompanied by reductions of β 3 -adrenoreceptor mediated DSM relaxations (6).…”

Section: Introductionmentioning

confidence: 99%

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Effect of acute administration of sildenafil to rats with detrusor overactivity induced by chronic deficiency of nitric oxide

et al. 2013

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Purpose: Recently, the effect of phosphodiesterase inhibitors (PDE5i) in the lower urinary tract symptoms (LUTS) associated to benign prostatic hyperplasia have been studied thoroughly. However, it remains unclear how the PDE5i improve LUTS. Therefore, the aim of the present study was to evaluate the potential of acute administration of the PDE5i sildenafil to improve detrusor overactivity (DO) induced by N ω -nitro-L -arginine methyl ester hydrochloride (L-NAME), an nitric oxide sinthase (NOS) inhibitor, in rats. Materials and Methods: Twenty-seven MALE adult Wistar Rats were divided into the following groups: (1) control, (2) L-NAME, (3) sildenafil alone, and (4) L-NAME + sildenafil. The NOS blocker L-NAME (20 mg/rat/day) was given in the drinking water. Sildenafil (100μg/kg) was administrated intravenously (i.v.) acutely, diluted in cremophor, propylene glycol and water. All animals underwent to anesthetized cystometograms. Results: The chronic and systemic administration of L-NAME markedly increased the number of non voiding contractions (2.62 (± 0.89)), and frequency of micturition (1.97 (± 0.78)), as well increased volume threshold (2.83 mL (± 1.64)) compared with control group, the number of non voiding contractions (1.17 (± 0.75)), frequency of micturition (1.08 (± 0.65)) and volume threshold (1.16 mL (± 0.38)), p < 0.001, p = 0.01, and p = 0.04, respectively. Sildenafil infusion decreased the number of micturition cycles significantly from the baseline to end point (-0.93 (± 0.34)) in nitric oxide (NO) deficient animals compared with sildenafil infusion alone (control) in animals with normal NO level (0.13 (± 0.25)), p = 0.03. Conclusion: Systemic reduction of nitric oxide causes detrusor overactivity and acute infusion of sildenafil reduces the number of micturition cycles in chronic NO-deficient rats.

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of acute administration of sildenafil to rats with detrusor overactivity induced by chronic deficiency of nitric oxide

et al. 2013

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“…This finding was also similar to an organ bath study that evaluated bladder of rats submitted to chronic NO deficiency induced by daily administration of L-NAME. An increased contractile response of the detrusor muscle to muscarinic receptors and reduced relaxation mediated by adrenergic receptors was noted (4). In this study, it was also observed an increase in VT in animals with chronic deficiency of NO similarly to a previous study (18).…”

Section: Discussionsupporting

confidence: 85%

“…A study showed that 4-week treatment with the NO synthase blocker L-Nitroarginine methyl ester (L-NAME) causes in vitro DSM supersensitivity to muscarinic agonists via increase in the levels of [H3]-inositol-phophate, accompanied by reduction of ß3-adrenoreceptor mediated DSM relaxations (4).…”

Section: Introductionmentioning

confidence: 99%

Effects of chronic administration of tamsulosin and tadalafil, alone or in combination, in rats with bladder outlet obstruction induced by chronic nitric oxide deficiency

et al. 2014

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ARTICLE INFO ______________________________________________________________ ______________________Purpose: The aim of this study was to define if tadalafil causes detrusor muscle impairment and to observe the effect of combination of tadalafil with tamsulosin on the lower urinary tract of rats with bladder outlet obstruction (BOO) induced by chronic nitric oxide deficiency. Materials and Methods: Thirty-one male rats were randomized to following groups: 1 -control; 2 -L-Nitroarginine methyl ester (L-NAME); 3 -Tamsulosin + L-NAME, 4 Tadalafil+L-NAME; and 5 -Tamsulosin + Tadalafil + L-NAME. At the end of the treatment period (30 days), all animals were submitted to urodynamic study. Results:The administration of L-NAME increased the number of non-voiding contractions (NVC) (1.04 ± 0.22), volume threshold (VT) (1.86 ± 0.35), and micturition cycle (MC) (1.34 ± 0.11) compared with control (0.52 ± 0.06, 0.62 ± 0.06, and 0.67 ± 0.30), respectively. The administration of tamsulosin reduced the number of NVC (0.57 ± 0.42) and VT (0.76 ± 0.24 ) compared with L-NAME group. Co-treatment with tadalafil decreased the number of VT (0.85 ± 0.53) and MC (0.76 ± 0.22) compared with L-NA-ME group. The combination of tamsulosin with tadalafil improved the number of NVC (0.56 ± 0.18), VT (0.97 ± 0.52) and MC (0.68 ± 0.30) compared with L-NAME group. Conclusion: In rats with BOO induced by chronic nitric oxide deficiency, tadalafil did not cause impairment in detrusor muscle and seems to have an addictive effect to tamsulosin because the combination decreased non voiding contractions as well the number of micturition cycles.

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Long‐term administration of BAY 41‐2272 prevents bladder dysfunction in nitric oxide‐deficient rats

Mónica¹,

Reges²,

Cohen³

et al. 2010

Neurourology and Urodynamics

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Long‐term nitric oxide deficiency causes muscarinic supersensitivity and reduces β₃‐adrenoceptor‐mediated relaxation, causing rat detrusor overactivity

Cited by 46 publications

References 54 publications

Effect of acute administration of sildenafil to rats with detrusor overactivity induced by chronic deficiency of nitric oxide

Effect of acute administration of sildenafil to rats with detrusor overactivity induced by chronic deficiency of nitric oxide

Effects of chronic administration of tamsulosin and tadalafil, alone or in combination, in rats with bladder outlet obstruction induced by chronic nitric oxide deficiency

Long‐term administration of BAY 41‐2272 prevents bladder dysfunction in nitric oxide‐deficient rats

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Long‐term nitric oxide deficiency causes muscarinic supersensitivity and reduces β3‐adrenoceptor‐mediated relaxation, causing rat detrusor overactivity

Cited by 46 publications

References 54 publications

Effect of acute administration of sildenafil to rats with detrusor overactivity induced by chronic deficiency of nitric oxide

Effect of acute administration of sildenafil to rats with detrusor overactivity induced by chronic deficiency of nitric oxide

Effects of chronic administration of tamsulosin and tadalafil, alone or in combination, in rats with bladder outlet obstruction induced by chronic nitric oxide deficiency

Long‐term administration of BAY 41‐2272 prevents bladder dysfunction in nitric oxide‐deficient rats

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Long‐term nitric oxide deficiency causes muscarinic supersensitivity and reduces β₃‐adrenoceptor‐mediated relaxation, causing rat detrusor overactivity