Abstract
Sildenafil slows down the gastric emptying of a liquid test meal in awake rats and inhibits the contractility of intestinal tissue strips. We studied the acute effects of sildenafil on in vivo intestinal transit in rats. Fasted, male albino rats (180-220 g, N = 44) were treated (0.2 mL, iv) with sildenafil (4 mg/kg) or vehicle (0.01 N HCl). Ten minutes later they were fed a liquid test meal (99m technetium-labeled saline) injected directly into the duodenum. Twenty, 30 or 40 min after feeding, the rats were killed and transit throughout the gastrointestinal tract was evaluated by progression of the radiotracer using the geometric center method. The effect of sildenafil on mean arterial pressure (MAP) was monitored in a separate group of rats (N = 14). Data (medians within interquartile ranges) were compared by the Mann-Whitney U-test. The location of the geometric center was significantly more distal in vehicle-treated than in sildenafil-treated rats at 20, 30, and 40 min after test meal instillation (3.3 (3.0-3.6) vs 2.9 (2.7-3.1); 3.8 (3.4-4.0) vs 2.9 (2.5-3.1), and 4.3 (3.9-4.5) vs 3.4 (3.2-3.7), respectively; P < 0.05). MAP was unchanged in vehicle-treated rats but decreased by 25% (P < 0.05) within 10 min after sildenafil injection. In conclusion, besides transiently decreasing MAP, sildenafil delays the intestinal transit of a liquid test meal in awake rats.
Highlights
Sildenafil citrate belongs to a class of compounds called phosphodiesterase (PDE) inhibitors
Since the gastrointestinal transit rate results from a complex interplay between gastric tonus, distal stomach phasic activity and resistance and propulsion offered by the small intestine [9], we measured the effect of sildenafil on the small bowel intestinal transit of a liquid test meal in awake rats
Intestinal transit was studied by scintigraphy, which allows the determination of the fractional retention of a radioactive marker throughout the gastrointestinal tract
Summary
Sildenafil citrate belongs to a class of compounds called phosphodiesterase (PDE) inhibitors. MAP remained within stable levels (P < 0.05) throughout the experiments (96.0 ± 3.5, 95.2 ± 3.4, 90.1 ± 3.0, 98.0 ± 3.2, 97.4 ± 3.6, 98.0 ± 3.0 mmHg, respectively for basal, vehicle injection, gavage feeding, and 20-, 30-, and 40-min postprandial intervals). Sildenafil treatment induced a significant but short-lived arterial hypotension (a 25% drop at nadir) from the respective basal MAP values (100.2 ± 3.0 mmHg).
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