Журнал новых физиотерапевтических методов

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Effects of Citrulline Combined with Tadalafil on Monocrotaline-Induced Pulmonary Hypertension in Rats Compared with Arginine

Fuminobu Ishikura, Mai Egawa, Yuri Takano, Kota Kumagai, Takashi Suzuki and Masahiko Morita

Purpose: Tadalafil, phosphodiesterase5 (PDE5) inhibitor, was reported to have a therapeutic effect on pulmonary hypertension (PH) and citrulline is an amino acid to dilate arteries as an extracellular supplement to improve nitric oxide (NO) production. Therefore, it is expected that combination of tadalafil and citrulline exert a stronger effect for PH. The aim of this study is to evaluate the combination effects of tadalafil and citrulline on monocrotaline (MCT) -induced PH in rats compared with the combination effects of tadalafil and arginine.

Methods: We used 4-week-old male SD rats which developed PH by 5-times subcutaneous injection of MCT. We evaluated heart function by echocardiography and calculated the ratio of RV to LV weight of heart before and after 6-times administration per two weeks of saline, tadalafil alone, citrulline alone and tadalafil and citrulline or arginine.

Results: The survival rate of tadalafil and citrulline administration was 91.7%, which was higher than other groups. The ratio of RV to LV weight in a tadalafil group and a tadalafil+citrulline group were significantly lower than other 3 groups.

Conclusion: Combination therapy of tadalafil and citrulline useful to prevent deterioration of pulmonary hypertension and improve survival rate compared with concomitant use of arginine.