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 100 mg/kg/4 hr) 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+/-0.17 micro g/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 micro g/mL), and thrombin-anti-thrombin complex (TAT) levels were significantly increased in rats receiving 20mg/kg/4 hr or greater doses of L-NAME (4.5+/-1.1, 4.7+/-1.4, 18.7+/-4.9, 42.5+/-4.0 ng/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, com-pared with control levels: 0.0+/-0.0%). Renal dysfunction and hepatic dysfunction were observed in rats receiving 20mg/kg/4 hr or greater, or 100mg/kg/4 hr, 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.
Asakura
Hidesaku
H
Department of Internal Medicine (III) Kanazawa University School of Medicine Takaramachi 13-1, Kanazawa Ishikawa 920-8641, Japan. hasakura@med3.m.kanazawa-u.ac.jp
Okudaira
Mariko
M
Ontachi
Yasuo
Y
Mizutani
Tomoe
T
Omote
Mika
M
Yoshida
Tomotaka
T
Kaneda
Minori
M
Yamazaki
Masahide
M
Morishita
Eriko
E
Takami
Akiyoshi
A
Miyamoto
Ken-ichi
K
Nakao
Shinji
S
D000818:Animals; D000991:Antithrombins / Q000737:chemistry; D001158:Arteries / Q000187:drug effects / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000378:metabolism; D005337:Fibrin / Q000737:chemistry; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis
D000991:Antithrombins; D005343:Fibrinolytic Agents; D009569:Nitric Oxide; D005337:Fibrin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D019331:NG-Nitroarginine Methyl Ester