埼玉医科大学雑誌 第31巻 第1号 (2004年1月) 41-54頁 ◇論文(図表を含む全文)は，PDFファイルとなっています．
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Effects of Estrogen on the Process of Cardiac Remodeling and Nephrosclerosis in Dahl Hypertensive Rats with Heart Failure
Rie Fukushima （Department of Nephrology, Saitama Medical School, Moroyama, Iruma-gun, Saitama 350-0495, Japan）
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<0.01 vs. OVX: 26＋/−3%) and cardiac hypertrophy, although blood pressure remained at the levels of 168＋/−8 mmHg. 4. In the heart obtained from EST rats, expression of ecNOS-mRNA was significantly increased and ACE-mRNA was significantly suppressed compared to HS. 5. In HS rats, urinary excretion of protein was increased (182.2＋/−40.2 mg/day). Ovariectomy induced the reduction of urinary excretion of protein (125.4＋/−23.4 mg/day) and estrogen supplementation induced a significant increases of urinary excretion of protein (352.2＋/−48.0 mg/day). 6. Light microscopic findings in the kidney showed glomerulosclerosis and interstitial fibrosis in HS rats. Estrogen supplementation induced the aggravation of glomerulosclerosis and interstitial fibrosis accompanied with microangiopathy and thrombosis. Conclusion: These data indicate that estrogen might protect the development of cardiac hypertrophy and consuming heart failure. However, estrogen promotes microangiopathy and thrombosis in the kidney with progression of kidney insufficiency in Dahl-S rats with heart failure.
Keywords: Hypertension, Myocardial Infarction, salt-sensitivity
J Saitama Med School 2004;31:41-54
(Received December 10, 2003)