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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To evaluate the effect of low molecular weight heparin (LMWH) oncardiovascular remodeling induced by long term inhibition of nitric oxide synthase withN-nitro-L-arginine methyl ester (L-NAME), 40 male Sprague-Dawley rats were randomlydivided into four groups: the control group (n=10) that received 0.9% saltsolution; the L-NAME group (n=10) that received 30 mg/kg/day of L-NAME, theLMWH3000 group (n=10) that received 30 mg/kg/day of L-NAME and 4 mg/kg/dayof 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).All agents, including saline, were administered intraperitoneally by implantation ofosmotic mini pumps. Systolic blood pressure was measured by the tail-cuff method ontreatment days 1,7, 14, and 28, and histological examination of harvested cardiac tissueand coronary arteries was performed on day 28. Systolic blood pressure was greater inthe L-NAME, LMWH3000 and LMWH6000 groups when compared with the controlgroup. There were no significant differences in activated coagulation time (ACT)when comparing the four groups. Medial smooth muscle cell proliferation and hypertrophyand increases in perivascular and myocardial fibrosis were observed in the L-NAMEgroup compared with the control group. Further, these changes were inhibited by thecoadministration of LMWH3000 or LWMH6000. This study demonstrates that LMWHprevents cardiovascular remodeling induced by L-NAME in rat hearts independent of itsanticoagulant activity. Low molecular weight heparin prevents cardiovascular remodeling
秋田大学の論文

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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