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

Abstract

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.

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

“…Thus, PDE5i increasing cGMP can probably explain the reduction in VT (decrease urethral resistance) and MC (relaxation of detrusor) observed in this study. This finding was comparable to other study that concluded that acute administration of sildenafil decreases the number of MC (18). As tadalafil did not decrease detrusor pressure (LP or PP) become +P < 0.05 comparing L-NAME with control; *P < 0.05 comparing Tadalafil and Tamsulosin/Tadalafil groups with L-NAME.…”

“…Increase in NVC and MC in experimental in vivo studies have been associated with DO (18). 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). There are two theories that could explain this observation: increased urethral resistance or detrusor impairment.…”

“…Detrusor overactivity was defined as increase of NCV or MC. Bladder outlet obstruction (BOO) was considered as increased VT with normal or increased TP (18). Detrusor hypocontratility was defined as increased VT associated with decreased TP.…”

Effects of nitric oxide inhibitors in mice with bladder outlet obstruction

“…Micturition frequency was measured considering the number of micturition cycles within 30 minutes. Threshold pressure was defined as the pressure immediately before micturition (8). Bladders of mice used for cystometry were not used in the other experiments.…”