Effect of diminazene on monocrotalin-induced pulmonary hypertension rat model

Abstract

Aim: Pulmonary arterial hypertension (PAH) is a serious disease with a poor prognosis. We aimed to research effect of diminazene (DMZ), as an agent increasing enzymatic activity of angiotensin converting enzyme 2, on PAH. Materials and Methods: In total, 32 nine-week-old male Wistar 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 intraperitoneallyin 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 all of the rats was analyzed through a modified forced swimming test. After measuring right ventricular systolic pressure using an open-chest method, the heart and lungs were analyzed histopathologically in terms of right ventricle hypertrophy and pulmonary vascular remodeling. Results: On the 35th day, the mortality rate was zero in the control group, 53.1% in the PAH group, and 14.3% in thePAH+DMZ group. A statistically significant decrease was observed in mortality rates with DMZ treatment, and significant recovery was noted in terms of median life spans (p = 0.16 and p = 0.01, respectively). DMZ treatment 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). Conclusion: DMZ prolonged life expectancy in PAH and decreased pulmonary arterial muscularization. Thus, it may be a new candidate treatment for PAH.