Low Molecular Weight Heparin Prevents Cardiovascular Remodeling Induced by the Long-Term Inhibition of Nitric Oxide Synthase with N-Nitro-L-Arginine Methyl Ester in Rat Hearts-猫眼课题宝

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2004-12

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H. Hasegawa;Takashi Saito;Yoshimasa Fujiwara;F. Kurokawa;T. Kosaka;Hiroyuki Watanabe;K. Iino;Masaru Ishida;T. Koyama;Kouichi Kawamura;H. Masuda;M. Miura;Hiroshi Ito

为探讨低分子量肝素（LMWH）对N-硝基-L-精氨酸甲酯（L-NAME）长期抑制一氧化氮合酶（NOS）诱导的心血管重构的影响，将40只雄性SD大鼠随机分为4组：对照组（n=10），给予0.9%生理盐水; L-NAME组（n=10）接受L-NAME 30 mg/kg/d，LMWH 3000组（n=10）接受L-NAME 30 mg/kg/d和LMWH 4 mg/kg/d（分子量（M.W.）的3000）和LMWH 6000组（n=10），所述LMWH 6000组接受30 mg/kg/天的L-NAME和4 mg/kg/天的LMWH（M.W.6000）。通过植入渗透微型泵腹腔内给予包括生理盐水在内的所有药物。在治疗第1、7、14和28天通过尾套法测量血压，并在第28天对收集的心脏组织和冠状动脉进行组织学检查。LMWH 3000和LMWH 6000组与对照组比较，活化凝血时间（ACT）无显著性差异，LMWH 3000组和LMWH 6000组中膜平滑肌细胞增生肥大，血管周围和心肌纤维化增加，LMWH 3000或LWMH 6000可抑制L-NAME诱导的大鼠心血管重构，LMWH对L-NAME诱导的心血管重构的抑制作用与其抗凝活性无关。―221―（55）秋田医学杂志31：221- 230，2004年秋田大学

To evaluate the effect of low molecular weight heparin(LMWH)on cardiovascular remodeling induced by long term inhibition of nitric oxide synthase with N-nitro-L-arginine methyl ester(L-NAME),40 male Sprague-Dawley rats were randomly divided into four groups:the control group(n=10)that received 0.9% salt solution;the L-NAME group(n=10)that received 30 mg/kg/day of L-NAME,the LMWH3000 group(n=10)that received 30 mg/kg/day of L-NAME and 4 mg/kg/day of LMWH (molecular weight(M.W.)of 3000)and the LMWH6000 group(n=10) that received 30 mg/kg/day of L-NAME and 4 mg/kg/day of LMWH (M.W.6000). Al agents,including saline,were administered intraperitonealy by implantation of osmotic mini pumps.Systolic blood pressure was measured by the tail-cuff method on treatment days 1,7,14,and 28,and histological examination of harvested cardiac tissue and coronary arteries was performed on day 28.Systolic blood pressure was greater in the L-NAME,LMWH3000 and LMWH6000 groups when compared with the control group.There were no significant differences in activated coagulation time(ACT) when comparing the four groups.Medial smooth muscle cel proliferation and hypertrophy and increases in perivascular and myocardial fibrosis were observed in the L-NAME group compared with the control group.Further,these changes were inhibited by the coadministration of LMWH3000 or LWMH6000.This study demonstrates that LMWH prevents cardiovascular remodeling induced by L-NAME in rat hearts independent of its anticoagulant activity. ―221― (55) Akita J Med 31:221-230,2004 Akita University

Low Molecular Weight Heparin Prevents Cardiovascular Remodeling Induced by the Long-Term Inhibition of Nitric Oxide Synthase with N-Nitro-L-Arginine Methyl Ester in Rat Hearts

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