PROTECTION BY ESTRADIOL AGAINST THE DEVELOPMENT OF CARDIOVASCULAR CHANGES ASSOCIATED WITH MONOCROTALINE PULMONARY-HYPERTENSION IN RATS

1 We studied the effects of oestradiol 17beta on the development of pu lmonary vascular changes and right ventricular (RV) hypertrophy in res ponse to monocrotaline in male Sprague-Dawley rats. 2 Rats were treate d with either placebo or oestradiol 17beta (10 mg) in the form of slow release pellets implanted subcutaneously 48 h before monocrotaline ad ministration. Rats were injected with either saline or a single dose o f monocrotaline (60 mg kg-1, i.m.). Pulmonary vascular changes and RV hypertrophy were studied at 4 weeks following monocrotaline administra tion. 3 Monocrotaline induced a significant increase in the ratio of r ight ventricle (RV) to left ventricle-plus-septum (LV + S) weights. Mo nocrotaline-treated rats also showed significant myointimal proliferat ion in small pulmonary arteries, decrease of arterial numbers and incr ease in the number of abnormal alveolar macrophages. 4 Oestradiol 17be ta attenuated myointimal hyperplasia in pulmonary vessels, decreased t he RV/(LV + S) ratio in monocrotaline-treated rats. Oestradiol 17beta had no significant effect on control animals. 5 Oestradiol treatment p revented the increase in lung wet to dry weight ratio, observed 7 days post monocrotaline administration. 6 These results suggest that oestr adiol 17beta protects against the pulmonary vascular remodelling and R V hypertrophy associated with monocrotaline-induced pulmonary hyperten sion in the rat. Oestradiol also protects against microvascular leak o bserved in the early days of lesion.