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Hidesaku Asakura, Mariko Okudaira, Yasuo Ontachi, Tomoe Mizutani, Mika Omote, Tomotaka Yoshida, Minori Kaneda, Masahide Yamazaki, Eriko Morishita, Akiyoshi Takami, Ken-ichi Miyamoto, Shinji Nakao
Antithrombotic role of nitric oxide in rats under physiological conditions
Although sepsis-induced release of nitric oxide (NO) is known to have an antithrombotic effect, it is unknown if NO exerts this same effect under physiological conditions.We have there-fore attempted to determine whether or not NO protects against thrombus formation in normal Wistar rats injected with various amounts (0.8, 4.0, 20.0 and 100mg/kg/4hr) of L-NAME (N (omega)-nitro-l-arginine methyl ester), an NO synthase inhibitor, via the tail vein. Plasma levels of D-dimer fragments of fibrin were significantly increased in rats receiving L-NAME (0.210.04, 0.220.05, 0.260.07, 0.590.17g/mL, meansSE; p<0.05, 0.05, 0.05, 0.01: L-NAME 0.8, 4, 20, 100, respectively, compared with control levels: <0.06 g/mL), and thrombin-anti-thrombin complex (TAT) levels were significantly increased in rats receiving 20mg/kg/4hr or greater doses of L-NAME (4.51.1, 4.71.4, 18.74.9, 42.54.0ng/mL, NS, NS, p<0.05, 0.01, respectively, compared with control levels: 3.81.2 ng/mL). Glomerular fibrin deposition was increased in a dose-dependent manner in rats receiving L-NAME (6.81.5, 13.91.6, 32.42.6, 49.25.2%, p<0.05, 0.05, 0.01, 0.01, respectively, com-pared with control levels: 0.00.0%). Renal dysfunction and hepatic dysfunction were observed in rats receiving 20mg/kg/4hr or greater, or 100mg/kg/4hr, doses of L-NAME, respectively. Mean blood pressure was also elevated in rats receiving L-NAME in a dose-dependent manner. These findings suggest that NO, in addition to regulating blood pressure, is involved in prevention of thrombus formation under physiological circumstances.
Thrombosis and Haemostasis, Schattauer
Print ISSN: 0340-6245
Volume: 91, 01/2004
Pages: 071 - 075