Endothelium-dependent relaxation of isolated splanchnic arteries from cirrhotic patients: Role of reactive oxygen species.
OBJECTIVE
To examine the endothelium-dependent relaxation of splanchnic arteries during cirrhosis as well as the role of reactive oxygen species in this relaxation using hepatic arteries from cirrhotic patients undergoing liver transplantation and mesenteric arteries from liver donors.


METHODS
Arterial segments 3 mm long were mounted in organ baths for isometric tension recording and precontracted with the thromboxane A(2) analog U46619 (10(-7)-10(-6) M).


RESULTS
The relaxation to acetylcholine (10(-8)-10(-4) M), but not to sodium nitroprusside (10(-8)-10(-4) M) was lower in hepatic arteries. The inhibitor of nitric oxide synthesis, N(omega)-nitro-l-arginine methyl ester (l-NAME, 10(-4) M), the inhibitor of cyclooxygenase, meclofenamate (10(-5) M), or l-NAME (10(-4) M) + meclofenamate (10(-5) M) diminished the relaxation to acetylcholine only in mesenteric arteries. l-NAME (10(-4) M) + meclofenamate (10(-5) M) combined with charybdotoxin (10(-7) M) + apamine (10(-6) M) inhibited the relaxation toacetylcholine in both types of arteries, and this inhibition was greater than with l-NAME + meclofenamate. The scavenger of hydrogen peroxide, catalase (1000 U/mL), the superoxide dismutase mimetic, tiron (10(-2) M) or the inhibitor of NAD(P)H oxidase, diphenyleneiodonium (5 x 10(-6) M), but not the inhibitor of superoxide dismutase, diethyldithiocarbamate (10(-3) M) potentiated the acetylcholine-induced relaxation only in hepatic arteries. l-NAME did inhibit the relaxation to acetylcholine in hepatic arteries pretreated with catalase or tiron.


CONCLUSIONS
Cirrhosis may decrease endothelial release and/or bioavailability of nitric oxide and prostacyclin in splanchnic arteries, which might be caused partly by increased production of reactive oxygen species.
Salcedo
Adely
A
Department of Physiology, University Hospital 'Puerta de Hierro', Faculty of Medicine, Autonomous University, Madrid, Spain.
Garijo
Jesús
J
Monge
Luis
L
Sánchez
Ana
A
Fernández
Nuria
N
García-Villalón
Angel L
AL
Turrión
Víctor S
VS
Cuervas-Mons
Valentín
V
Diéguez
Godofredo
G