Heart failure caused by right ventricular hypertrophy and the fibrosis is a major cause of death in pulmonary hypertension. It has been reported that certain angiotensin AT₁ receptor blocker possesses inhibitory effect on cardiovascular remodeling. Thus, in the present study, we investigated whether olmesartan, an angiotensin AT₁ receptor blocker, could attenuate right ventricular hypertrophy and/or fibrosis using rats with monocrotaline-induced pulmonary hypertension.
Male Sprague-Dawley rats (5-week-old) were administered single subcutaneous injection of monocrotaline (60 mg/kg) and induced pulmonary hypertension. Olmesartan continuously infused subcutaneously for 4 weeks by use of an osmotic mini pump. The estimated dosage of olmesartan during the experimental period was around 3 mg/kg/day.
Treatment with olmesartan failed to improve right venricular hypertrophy, whereas it reduced right ventricular fibrosis in the monocrotaline-treated rats. Moreover, enhanced expression of fibrosis-related proteins including IL-6, IL-1beta, GDF15, CTGF, and MMP9 the rats was not observed in the olmesartan-treated rat right ventricles. These results suggest that olmesartan has a potential to be a therapeutic agent against pulmonary hypertension.