Prolonged bleeding time in experimental cirrhosis: role of nitric oxide.
OBJECTIVE
Nitric oxide is a powerful in vitro inhibitor of platelet adhesion and aggregation. Our aim was to investigate whether the in vivo inhibition of nitric oxide release shortens bleeding time, in rats with cirrhosis induced by chronic bile duct ligation.


METHODS
Mean arterial pressure and bleeding time were measured under basal conditions and 5, 15 and 30 min after administration of vehicle (0.9% saline) or an inhibitor of nitric oxide synthesis, Nw-nitro-L-arginine (5 mg/kg, iv). Mean arterial pressure was measured with an intra-arterial catheter and bleeding time with a standardized Simplate device.


RESULTS
Cirrhotic rats showed a lower mean arterial pressure (116+/-4 mmHg) and a prolonged bleeding time (177+/-40 s) compared to control animals (133+/-6 mmHg and 95+/-12 s, respectively, p<0.01). In cirrhotic rats, Nw-nitro-L-arginine significantly increased mean arterial pressure (from 116+/-5 to 141+/-11 mmHg, p<0.05) and completely normalized bleeding time (from 170+/-39 to 103+/-21 s, p<0.05) 15 min after administration. Pretreatment with L-arginine (300 mg/kg, iv) prevented the hemodynamic and hemostatic changes induced by Nw-nitro-L-arginine. A trend to normalize platelet adhesion was observed in cirrhotic rats after the inhibition of nitric oxide production. In control animals, Nw-nitro-L-arginine increased mean arterial pressure, while no effect on bleeding time was observed.


CONCLUSIONS
These findings support the concept that nitric oxide may be a mediator in the bleeding time abnormalities associated with experimental cirrhosis.
Albornoz
L
L
Sección de Higado, Hospital Italiano, Buenos Aires, Argentina.
Bandi
J C
JC
Otaso
J C
JC
Laudanno
O
O
Mastai
R
R
D000818:Animals; D001760:Bleeding Time; D006439:Hemodynamics; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D009569:Nitric Oxide