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Sildenafil citrate, a potent and selective inhibitor of phosphodiesterase type-5, is used clinically to treat erectile dysfunction and pulmonary arterial hypertension. We investigated the effect of sildenafil citrate on brain central fatigue through serotonin (5-hydroxytryptamine, 5-HT) synthesis after exhaustive swimming exercise in rats. The rats in the sildenafil citrate-treated groups received sildenafil citrate orally once a day for 14 consecutive days at respective dosage. On the 14 days after starting experiment, each animal was submitted to swimming test with intensity equivalent to overload. The exhaustion was defined as a state in which coordinated movements did not return to the water surface for breathing within 10 sec. Immunohistochemistry for 5-HT, tryptophan hydroxylase (TPH), and western blot for serotonergic type 1A (5-HT1 A ) receptor and 5-HT transporter (5-HTT) were performed. Exhaustive swimming exercise increased 5-HT and TPH expressions in the dorsal raphe and sildenafil citrate suppressed 5-HT and TPH expressions in the exhaustive swimming exercise rats. Exhaustive swimming exercise increased 5-HT1 A receptor and 5-HTT expressions in the dorsal raphe and sildenafil citrate suppressed 5-HT1 A receptor and 5-HTT expressions in the exhaustive swimming exercise rats. The significant suppressing effect appeared in the 20-mg/kg sildenafil citrate. Sildenafil citrate might be proposed as a potential ergogenic aid through anticentral fatigue.

Effect of sildenafil citrate on brain central fatigue after exhaustive swimming exercise in rats