By treating cirrhotic patients with fluoroquinolone to decrease circulating endotoxin and nitric oxide (NO) production, Chin-Dusting and colleagues [1] sought to reduce the impaired vascular response of the forearm circulation. Thus, it has been hypothesized that reduced reticuloendothelial function of the liver and portosystemic shunting permit endotoxin that originates from the gut to reach the systemic circulation and increase the release of NO (through the inducible NO synthase). Consequently, excess NO production may induce hypotension and impair the vascular response to various vasoactive drugs. As has been previously shown, NO production is increased in cirrhotic patients because plasma nitrite or nitrate concentrations and exhaled NO concentrations are higher in these patients than in controls. However, in contrast to the findings of a recent study [2] in which colistin was used to decrease plasma endotoxin and nitrite or nitrate concentrations in cirrhotic patients, fluoroquinolone cannot decrease nitrite or nitrate concentrations. Moreover, Chin-Dusting and colleagues did not measure the effect of the antibiotic on plasma endotoxin. Of note, the vasoconstrictor effect of N^G -monomethyl-L-arginine is higher in cirrhotic patients than in controls, and cirrhotic patients treated with fluoroquinolone recover a normal response to the vasoconstrictor. The endothelium-dependent vasodilation following acetylcholine administration is enhanced, as already shown [3], but fluoroquinolone does not modify this enhanced response.

The hypothesis that endotoxin (and NO) is responsible for the impaired vascular reactivity in cirrhosis may be partly incorrect for two reasons. First, plasma nitrite or nitrate concentrations are much higher in septic patients (approximately 100 µmol/L) [4] than in cirrhotic patients (approximately 40 µmol/L). Second, the endothelium-dependent vasodilation following acetylcholine administration is enhanced in cirrhosis but decreased in endotoxemia [5]. Thus, the increased NO production in cirrhosis seems limited; additional mechanisms may explain the cardiovascular abnormalities of the disease.