Premium
Inhibitory effect of sildenafil on rat duodenal contractility In vitro : Putative cGMP involvement
Author(s) -
Araújo Paula Vasconcelos,
Clemente Cristiano Magalhães,
Da Graça José Ronaldo Vasconcelos,
Rola Francisco Hélio,
De Oliveira Ricardo Brandt,
Dos Santos Armênio Aguiar,
Magalhães Pedro Jorge Caldas
Publication year - 2005
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2005.04170.x
Subject(s) - sildenafil , papaverine , contraction (grammar) , endocrinology , medicine , acetylcholine , chemistry , contractility , zaprinast , nitric oxide , guanylate cyclase
SUMMARY 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 activity in 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 IC 50 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 IC 50 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 EC 50 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 EC 50 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 EC 50 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 segments in 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.