Inhibitory effect of sildenafil on rat duodenal contractilityIn vitro: Putative cGMP involvement.

1. Sildenafil citrate (Viagra™; Pfizer, Sandwich, Kent, UK), a phosphodiesterase 5 inhibitor, rises cGMP levels in smooth muscle cells. It relaxes both vascular and visceral smooth muscle. In order to assess the intestinal effects of sildenafil, we decided to investigate its actions on rat duodenal motor activityin vitro.2. In isolated duodenal segments maintained in Tyrode's solution, sildenafil exhibited a concentration-dependent antispasmodic effect on acetylcholine (ACh)-induced phasic contractions, with an IC₅₀ value of 26.7 µmol/L (95% confidence interval (CI) 2.0–55.3 µmol/L).3. Sildenafil also relaxed the carbamylcholine (CCh)-induced sustained contraction with an IC₅₀ of 16.2 µmol/L (95% CI 9.5–27.6 µmol/L). Sildenafil produced significant additional relaxation of 25.2 ± 8.1% of the CCh-induced contraction, beyond basal tone.4. Sildenafil reduced the amplitude of spontaneous duodenal contractions with an EC₅₀ of 9.6 µmol/L (95% CI 5.7–16.2 µmol/L). This effect was significantly more potent than the effects of zaprinast and papaverine, which also reduced duodenal contractions with EC₅₀ values of 91.6 µmol/L (95% CI 46.0–182.2 µmol/L) and 78.5 µmol/L (95% CI 37.1–166.3 µmol/L), respectively.5. In preparations treated previously with methylene blue (10 μmol/L) or 1H-[1,2,4]oxadiazolo(4,3-a)quinoxalin-1-one (ODQ; 10 µmol/L), the EC₅₀ values for the sildenafil effect were significantly increased to 39.0 µmol/L (95% CI 23.9–63.4 µmol/L) and 43.8 µmol/L (95% CI 24.5–78.3 µmol/L), respectively. These values were significantly greater than those obtained with sildenafil alone.6. In conclusion, sildenafil has myorelaxant and antispasmodic effects on rat duodenal segmentsin vitro.The contractile inhibitory effect of sildenafil on rat isolated duodenum is probably due to intracellular cGMP accumulation as a result of its decreased degradation. [ABSTRACT FROM AUTHOR]