Protection by oestradiol against the development of cardiovascular changes associated with monocrotaline pulmonary hypertension in rats.
1. We studied the effects of oestradiol 17 beta on the development of pulmonary vascular changes and right ventricular (RV) hypertrophy in response to monocrotaline in male Sprague-Dawley rats. 2. Rats were treated with either placebo or oestradiol 17 beta (10 mg) in the form of slow release pellets implanted subcutaneously 48 h before monocrotaline administration. Rats were injected with either saline or a single dose of monocrotaline (60 mg kg-1, i.m.). Pulmonary vascular changes and RV hypertrophy were studied at 4 weeks following monocrotaline administration. 3. Monocrotaline induced a significant increase in the ratio of right ventricle (RV) to left ventricle-plus-septum (LV + S) weights. Monocrotaline-treated rats also showed significant myointimal proliferation in small pulmonary arteries, decrease of arterial numbers and increase in the number of abnormal alveolar macrophages. 4. Oestradiol 17 beta attenuated myointimal hyperplasia in pulmonary vessels, decreased the RV/(LV + S) ratio in monocrotaline-treated rats. Oestradiol 17 beta had no significant effect on control animals. 5. Oestradiol treatment prevented the increase in lung wet to dry weight ratio, observed 7 days post monocrotaline administration. 6. These results suggest that oestradiol 17 beta protects against the pulmonary vascular remodelling and RV hypertrophy associated with monocrotaline-induced pulmonary hypertension in the rat. Oestradiol also protects against microvascular leak observed in the early days of lesion.
Farhat
M Y
MY
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, D.C. 20007.
Chen
M F
MF
Bhatti
T
T
Iqbal
A
A
Cathapermal
S
S
Ramwell
P W
PW
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004343:Drug Implants; D004958:Estradiol / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced; D008297:Male; D016686:Monocrotaline; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011651:Pulmonary Artery / Q000473:pathology; D011652:Pulmonary Circulation / Q000187:drug effects; D011654:Pulmonary Edema / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004343:Drug Implants; D004958:Estradiol; D016686:Monocrotaline