Physiological and pathological effects of diminazene on pulmonary hypertension: a controlled rat model study


Sengul A., ARKAN S., VURAL Ç., Ozer C., Bayrak B., Tas A., ...More

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE, vol.9, no.2, pp.909-917, 2016 (SCI-Expanded) identifier identifier

Abstract

Objectives: To evaluate the effects of diminazene (DMZ) on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Methods: In total, 32 nine-week-old male Wistar-Albino rats (170-240 g) were divided into three groups: control (n=10), PAH (n=15), and PAH+DMZ groups (n=7). On the first day, 60 mg/kg MCT was injected intraperitoneally in the PAH and PAH+DMZ groups. On the 21st day, 15 mg/kg/day DMZ was injected, and the animals were followed for 35 days. On the 35th day, the exercise capacity of rats was analyzed through a modified forced swimming test. After measuring right ventricular systolic pressure using an open-chest method, right ventricle hypertrophy and pulmonary vascular remodeling were evaluated histopathologically. Results: On the 35th day, the mortality rate was zero in the control group, 53.1% in the PAH group, and 14.3% in the PAH+DMZ group. A significant decrease was observed in mortality rates with DMZ, and significant recovery was noted in median life spans (P=0.16 and P=0.01, respectively). DMZ had no significant effect on exercise capacity, right ventricle hypertrophy, or right ventricle systolic pressure, whereas there was significant recovery in pulmonary artery muscular layer thickness (P=0.046). Conclusions: DMZ prolonged life expectancy in PAH and decreased pulmonary arterial muscularization. Thus, it may be a new candidate treatment for PAH.