[Dexamethasone, an inhibitor of the expression of inducible nitric oxide synthase, does not modify the hyperdynamic state in cirrhotic rats].
Increased nitric oxide formation has been shown to be involved in the hyperdynamic circulation of portal hypertension. It has been proposed that it could be related to stimulation of the inducible nitric oxide synthase by endotoxin. Therefore, the aim of the present study was to evaluate whether dexamethasone treatment, an inhibitor of the expression of the inducible enzyme, ameliorates the hyperdynamic circulation observed in cirrhotic rats due to chronic bile duct ligation. Systemic and splanchnic hemodynamic parameters were measured after administration of dexamethasone (3 mg/kg/day during 3 days, i.p.) or its vehicle. In cirrhotic rats dexamethasone treatment caused a mild but not significantly higher mean arterial pressure in comparison with vehicle while similar values of cardiac output, peripheral vascular resistance, portal blood flow and portal pressure were observed in both group of animals. A significant body weight loss over the three days of treatment was observed in rats receiving dexamethasone. In sham-operated rats, dexamethasone administration caused similar changes as observed in cirrhotic animals. Endotoxemia was observed in five of six cirrhotic rats while it was not detected in the control group. Our results show that dexamethasone administration does not modify systemic and splanchnic hemodynamic parameters in endotoxemic cirrhotic rats. This finding suggests that stimulation of the inducible nitric oxide synthase may not play a role in the increased nitric oxide production in portal hypertension.
Albornoz
L
L
Sección de Hígado, Servicio de Clínica Médica, Hospital Italiano, Argentina.
Bandi
J C
JC
de las Heras
M
M
Mastai
R
R
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D004731:Endotoxins / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006439:Hemodynamics / Q000502:physiology; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D017082:Portal Pressure / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013152:Splanchnic Circulation / Q000502:physiology; D013154:Spleen / Q000502:physiology
D004731:Endotoxins; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D003907:Dexamethasone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat