Effects of nitric oxide inhibition by methylene blue in cirrhotic patients with ascites.
Increased endogenous nitric oxide production has been proposed as an important mediator of the peripheral arterial vasodilation and the hyperdynamic circulation in cirrhosis, whereas a decreased intrahepatic production of nitric oxide has been implicated in the pathogenesis of portal hypertension. The present study investigated the possible beneficial effects of methylene blue, which is a potent inhibitor of guanylate cyclase and nitric oxide synthase, on hyperdynamic circulation and renal function in cirrhotic patients with ascites together with the effects on portal hemodynamics. Twenty patients were evaluated at baseline and during 2 consecutive 4-hr periods after the administration of methylene blue at a dose of 3 mg/kg (10 patients) or placebo (10 patients). Mean arterial pressure, heart rate, cardiac output, systemic vascular resistance, plasma active renin, plasma aldosterone, plasma antidiuretic hormone, serum urea, serum creatinine, serum sodium, urinary flow rate, glomerular filtration rate, effective renal plasma flow, portal flow volume, and portal vein velocity were not modified by methylene blue or placebo. Urinary sodium excretion, fractional sodium excretion and serum nitric oxide levels were significantly decreased 4 hr after methylene blue administration (P < 0.05), to return toward basal levels over a further 4-hr period. It is concluded that methylene blue, at the dose used in the present study, has no effect on systemic and portal hemodynamics in cirrhotic patients with ascites. The reduction in renal sodium excretion, in the absence of changes in renal function and hemodynamics, suggests, at least partly, a direct antinatriuretic effect of methylene blue.
Kalambokis
Georgios
G
Department of Internal Medicine, Medical School, Ioannina, Greece.
Economou
Michalis
M
Fotopoulos
Andreas
A
Bokharhii
Jihad Al
JA
Christos
Pappas
P
Paraskevi
Kosta
K
Konstantinos
Papadimitriou
P
Katsaraki
Afroditi
A
Tsianos
Epameinondas V
EV
D000368:Aged; D001201:Ascites / Q000209:etiology / Q000503:physiopathology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008102:Liver Circulation / Q000187:drug effects; D008103:Liver Cirrhosis / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008751:Methylene Blue / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D011168:Portal System / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D014882:Water-Electrolyte Balance / Q000187:drug effects
D019001:Nitric Oxide Synthase; D008751:Methylene Blue