Low dose monocrotaline causes a selective pulmonary vascular lesion in male and female pneumonectomized rats

ABSTRACTPurpose/Aim: Low doses (30–80 mg/kg) of monocrotaline are commonly used to create experimental models of pulmonary hypertension in rats. At these doses, monocrotaline causes pulmonary endothelial apoptosis and acute lung injury which ultimately results in pulmonary vascular disease. Higher doses of monocrotaline (300 mg/kg) are known to create severe liver injury, but previous investigations with lower doses have not reported histology in other organs to determine whether the vascular injury with monocrotaline is pulmonary-selective or generalized. Materials and Methods: We therefore sought to determine whether monocrotaline caused extra-pulmonary injury at doses commonly used in pulmonary hypertension studies. We performed left pneumonectomy on young male and female rats before administering 50–60 mg/kg monocrotaline 7 days later. We monitored serum chemistry and urine dipsticks during the first 3 weeks while the animals developed pulmonary hypertension. After 3 weeks, we sacrificed animals and s...