Increased serum nitrite and nitrate levels in patients with cirrhosis: Relationship to endotoxemia

✍ Scribed by Dr. Carlos Guarner; German Soriano; Albert Tomas; Oriol Bulbena; Maria Teresa Novella; Joaquin Balanzo; Francisco Vilardell; Marisabel Mourelle; Salvador Moncada

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 546 KB
• Volume: 18
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840180520

✦ Synopsis

Nitric oxide derived from vascular endothelium is a potent vasodilator that plays a key role in the homeostasis of blood pressure. Because cirrhotic patients tend to have low arterial pressure, we measured in 51 patients and 10 control subjects serum nitrite and nitrate levels as an index of in uiuo nitric oxide generation. We also measured plasma endotoxin, a substance frequently increased in cirrhotic patients and known to induce nitric oxide synthesis. Cirrhotic patients showed significant increases in serum nitritehitrate and plasma endotoxin compared with controls. Values were particularly increased in patients with decompensated cirrhosis, as manifested by ascites with or without functional kidney failure. High serum nitritehitrate levels were associated with high plasma renin activity, high aldosterone and antidiuretic hormone levels and low urinary excretion of sodium. In addition, serum nitritehitrate levels significantly correlated with endotoxemia. Oral administration of colistin to 15 cirrhotic patients reduced significantly plasma endotoxin levels (p < 0.01) and serum nitritehitrate levels (p < 0.05). Because endotoxin enhances the expression of inducible nitric oxide synthase, our results suggest that circulating endotoxin in cirrhosis is responsible for excessive synthesis and release of nitric oxide by the vasculature. These findings might explain the hemodynamic dysfunction seen in cirrhotic patients. (HEPATOLOGY 1993; 18: 1139-1143.) Cirrhotic patients exhibit characteristic hemodynamic dysfunction manifested by tendency to arterial hypotension in a setting of high cardiac output and low systemic and splanchnic vascular resistance. These changes have been attributed to the excessive production or the decreased metabolism of an as-yetundetermined endogenous vasodilator substance. Several vasodilator agents have been implicated so far, including prostacyclin, glucagon, vasointestinal peptide,