Antithrombotic role of nitric oxide in rats under physiological conditions

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

doi:10.1160/TH03-05-0292

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 91(01): 71-75
DOI: 10.1160/TH03-05-0292

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Antithrombotic role of nitric oxide in rats under physiological conditions

Authors

Hidesaku Asakura

¹Department of Internal Medicine (III), Kanazawa University School of Medicine, Japan
Mariko Okudaira

²Hospital Pharmacy, Kanazawa University School of Medicine, Japan
Yasuo Ontachi

¹Department of Internal Medicine (III), Kanazawa University School of Medicine, Japan
Tomoe Mizutani

¹Department of Internal Medicine (III), Kanazawa University School of Medicine, Japan
Mika Omote

³Department of Laboratory Medicine, Kanazawa University School of Medicine, Japan
Tomotaka Yoshida

³Department of Laboratory Medicine, Kanazawa University School of Medicine, Japan
Minori Kaneda

¹Department of Internal Medicine (III), Kanazawa University School of Medicine, Japan
Masahide Yamazaki

¹Department of Internal Medicine (III), Kanazawa University School of Medicine, Japan
Eriko Morishita

¹Department of Internal Medicine (III), Kanazawa University School of Medicine, Japan
Akiyoshi Takami

¹Department of Internal Medicine (III), Kanazawa University School of Medicine, Japan
Ken-ichi Miyamoto

²Hospital Pharmacy, Kanazawa University School of Medicine, Japan
Shinji Nakao

¹Department of Internal Medicine (III), Kanazawa University School of Medicine, Japan

Abstract

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

Full Text

References

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