Antithrombotic role of nitric oxide in rats under physiological conditions

Summary

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 therefore 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 (0.21±0.04, 0.22±0.05, 0.26±0.07, 0.59±0.17µg/mL, means±SE; p<0.05, 0.05, 0.05, 0.01: L-NAME 0.8, 4, 20, 100, respectively, compared with control levels: <0.06 µg/mL), and thrombin-antithrombin complex (TAT) levels were significantly increased in rats receiving 20mg/kg/4hr or greater doses of L-NAME (4.5±1.1, 4.7±1.4, 18.7±4.9, 42.5±4.0ng/mL, NS, NS, p<0.05, 0.01, respectively, compared with control levels: 3.8±1.2 ng/mL). Glomerular fibrin deposition was increased in a dose-dependent manner in rats receiving L-NAME (6.8±1.5, 13.9±1.6, 32.4±2.6, 49.2±5.2%, p<0.05, 0.05, 0.01, 0.01, respectively, compared with control levels: 0.0±0.0%). 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.

Keywords

Nitric oxide - endothelium - L-NAME - thrombin-antithrombin III complex

• References

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