INHIBITION OF THE ISOLATED GUINEA-PIG URINARY BLADDER CONTRACTIONS BY SILDENAFIL (VIAGRA®): IN VITRO STUDY

Abstract

Abstract

Introduction: Overactive bladder is a medical condition which is characterized by an overactive detrusor,

involuntary contractions and/or incontinence. This condition is usually treated medically with anticholinergics

being the medication of choice in most cases. Recently, different pharmacological alternatives have been

defined in the treatment of detrusor instability. Among these, phosphodiesterases which play important roles

in the regulation of smooth muscle tone have been investigated in various clinical and experimental studies. In

the present study, we aimed to evaluate the effects of sildenafil (Viagra®) on the agonist induced contractility

of isolated Guinea-pig bladder.

Materials and Methods: A total of 10 adult Guinea-pigs weighing 400-450 gr were decapitated. Using a

midline abdominal incision the bladder was found, kept intact and isolated from the surrounding tissues. All

bladders were first placed into the saline solution and the strips were prepared. A 10x2 mm of isolated guineapig

bladder strip was prepared and placed into a jacketed organ bath containing physiological solution. A

passive tension of 1 gr was maintained. After the equilibration period acetylcholine (Ach) (10 μM), a strong

agonist, was added into the medium and the contractions were recorded. Following the contractions, sildenafil

(Viagra®) was added into the organ bath. Amplitude and frequency of contractions and area under the

contraction curves were evaluated by 10-min intervals.

Results: During equilibration period, small amplitude contractions were noted. After addition of ACh into

the jacketed organ bath which contains physiological saline solution, contractions with higher amplitude were

observed. Mean amplitude of contractions in isolated bladder strips after Ach was 1.81 g (±0.31 SEM).

Application of 0.5mM Sildenafil significantly reduced the mean amplitude of contractions and it was recorded

as 0.76 g (±0.15 SEM). Similarly, use of sildenafil also reduced the frequency of contractions.

Conclusion: Urge urinary incontinence is the most common form of urinary incontinence. Antimuscarinic

agents are widely used in the treatment of urgency and/or incontinence. However, they did not reach enough

efficacies because of their frequent side effects. In the present study, we investigated the efficacy of sildenafil

on pre-contracted isolated Guinea-pig bladder and determined that sildenafil significantly decreased both the

amplitude and the frequency of bladder contractions. The results of our study support the hypothesis that

phosphodiesterase inhibitors can be potentially helpful in the regulation of smooth muscle tone in various

tissues. However, there is need for further studies to reveal the exact roles of sildenafil and other

phosphodiesterase inhibitors in the treatment of overactive bladder.