心不全の形成過程におけるEstrogenの心臓リモデリングおよび腎組織にあたえる影響 : Dahl食塩感受性ラット心不全モデルを用いた検討

Objective: This study was attempted to elucidate the role of estrogen in the process of cardiac remodeling and nephrosclerosis in Dahl-S female rats with myocardial infarction. Methods: 48 Dahl-S rats with myocardial infarction (MI) were divided into four groups as follows; Group 1: MI rats with normal-salt diet (LS, 0.5%NaCl diet), Group 2: MI rats with high-salt diet (HS, 8%NaCl diet), Group 3: MI rats with ovariectomy (OVX, 8%NaCl diet), Group 4: OVX rats with supplementation of estrogen (EST) (8%NaCl diet, 17βestradiol 15 mg/pellet/90 days subcutaneous pellet). Myocardial infarction was made by coronary artery ligation. One week after surgery, ovariectomy was performed. After ovariectomy, high salt diet was fed and water was given ad libitum for 12 weeks. During the study, blood pressure (BP), heart rate, body weight, urine volume and urinary excretions of protein and sodium were measured every 2 weeks. Transthoracic echocardiogram (ejection fraction: EF, inter ventricular septal thickness: IVST) was performed under anesthesia at 12 weeks after surgery. At the end of the study, the heart and the kidney tissues were obtained for light microscopic examination and evaluations of the expression of mRNA of ACE (angiotensin converting enzyme) and ecNOS (nitric oxide synthase). Results: 1. Blood pressure in HS group showed a gradual elevation from 132＋/－8 to 152＋/－10 mmHg (12 weeks) accompanied with the reduction of EF (LS:64＋/－4% vs. HS:46＋/－3%, P<0.01) and increases of IVST. Ovariectomy induced significant reduction in EF (OVX:26＋/－3%, P<0.01 vs. HS) and increases in IVST without any significant changes in systemic BP (OVX:174＋/－12 mmHg). 2. Ovariectomy induced no significant changes in plasma concentration of ACE, PRA (plasma renin activity), angiotensin I and angiotensin II. 3. In the heart obtained from OVX rats, expression of ecNOS-mRNA was decreased and ACE-mRNA was increased. Ovariectomy induced aggravation of cardiac hypertrophy and fibrosis. Treatment with estrogen in OVX rats improved EF (EST:38＋/－4%, P