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 Nω-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: (11. Braun M, Wassmer G, Klotz T, Reifenrath B, Mathers M, Engelmann U: Epidemiology of erectile dysfunction: results of the ‘Cologne Male Survey'. Int J Impot Res. 2000; 12: 305-11.) control, (22. Blanker MH, Bohnen AM, Groeneveld FP, Bernsen RM, Prins A, Thomas S, et al.: Correlates for erectile and ejaculatory dysfunction in older Dutch men: a community-based study. J Am Geriatr Soc. 2001; 49: 436-42.) L-NAME, (33. Uckert S, Hedlund P, Andersson KE, Truss MC, Jonas U, Stief CG: Update on phosphodiesterase (PDE) isoenzymes as pharmacologic targets in urology: present and future. Eur Urol. 2006; 50: 1194-207; discussion 1207.) sildenafil alone, and (44. Mónica FZ, Reges R, Cohen D, Silva FH, De Nucci G, D'Ancona CA, et al.: Long-term administration of BAY 41-2272 prevents bladder dysfunction in nitric oxide-deficient rats. Neurourol Urodyn. 2011; 30: 456-60.) 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.
sildenafil nitrate [Supplementary Concept]; Nitric Oxide; Lower Urinary Tract Symptoms
