埼玉医科大学雑誌 第33巻 第3, 4号別頁 (2006年12月) T45-T53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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Thesis
モノクロタリン心不全モデルにおけるレニン−アンジオテンシン系遮断の効果

堀田 ゆりか
埼玉医科大学大学院臨床医学研究系 循環器内科学専攻
(指導 西村 重敬 教授)

医学博士 乙第1016号 平成18年3月24日 (埼玉医科大学)


Upregulated Neurohumoral Factors Play the Most Important in Left Ventricular Remodeling in Rats with Monocrotaline-Induced Pulmonary Hypertension
Yurika Hotta (Department of Cardiology, Saitama Medical University, Moroyama, Iruma-gun, Saitama 350-0495, Japan)

 Left ventricular remodeling might occur in patients with right ventricular hypertrophy and/or failure due to pulmonary hypertension, although LV is not under mechanical stress. We used rats with monocrotaline-induced pulmonary hypertension whether upregulated neurohumoral factors act to induce left ventricular remodeling and/or contribute to prognosis. Morphologic studies revealed a significant increase in left ventricle/body weight and right ventricle/body weight ratio in monocrotaline rats, indicating biventricular hypertrophy. RNase protection analysis clearly demonstrated upregulated mRNA of β myosin heavy chain, skeletal α-actin, and brain type natriuretic peptide (BNP) and downregulated mRNA of α myosin heavy chain in the free wall of left ventricle as well as in right ventricle, while the expressions of SERCA-2 and Na-Ca exchanger were not significantly changed. Plasma angiotensin II (ANG II), noradrenaline, and BNP levels were significantly increased. And also plasma BNP level was positively and significantly correlated with heart weight/body weight and plasma ANG II in monocrotaline rats. Kaplan Meier survival curve with Loglank analysis revealed that valsartan (AT1 blocker) significantly improved the prognosis of monocrotaline rats while carvedilol (αβblocker) did not significantly.
 We concluded that upregulated neurohumoral factors not direct mechanical stress played the most important role in the pathogensis of left ventricular hypertrophy and remodeling in right ventricular pressure overload model. ANG II appears to be the number one contributor among the various upregulated neurohumoral factors in our mode.
Keywords: Monocrotaline, Ventricular Remodeling, Angiotensin II, BNP, Valsartan, Carvedilol


(C) 2006 The Medical Society of Saitama Medical School