Effects of Various Doses of Monocrotaline Administration on the Development of Pulmonary Hypertension and its Regression in Rats

Abstract We observed the time course of hemodynamic and pathological changes after single injection of various dose of monocrotaline (Mct) to investigate the dose-dependent effects on the induction and regression of pulmonary hypertension in rat: A hundred four-week old male Sprague-Dowley rats were divided into five groups and each group, except the control group, received 10 mg, 20 mg, 30 mg or 40 mg/kg Mct, respectively. The experimental periods were nine weeks after monocrotaline injection. At the third, sixth and ninth week after treatment, the survival rate, cardiac catheterization and pathological changes were evaluated. All rats given 30 mg or 40 mg per kg of Mct died within five weeks. In the third week after the treatment, elevation of the right ventricular systolic pressure (RVSP), the grade of right ventricular hypertrophy (RVH) and histological change showed no significant difference among rats receiving 20, 30 or 40 mg/kg Mct injection. Almost all rats given 10 mg or 20 mg/kg Mct survived through the experimental period of nine weeks. Rats given 10 mg per kg of Mct did not develop pulmonary hypertension or pathological abnormalities in the lungs. Rats receiving 20 mg/kg Mct showed transient elevation of RVSP, RVH and pulmonary histological changes in the early phase, but these findings regressed by the ninth week of the experiment. Namely, rats which received 20 mg pr kg of Mct revealed transient elevation of right ventricular systolic pressure, right ventricular hypertrophy and pulmonary histological changes only in the early phase and these changes regressed gradually thereafter. These results indicate some kind of transient and reversible factor may play a role in the development and regression of Mct-induced pulmonary hypertension in rats.