Endothelin and nitric oxide in hepatorenal syndrome: a balance reset

The newly described endothelium-dependent vasoactive substances, nitric oxide and endothelins, have been the subject of intense investigative interest and have been demonstrated to promote a wide array of autocrine and paracrine functions. Recent data highlight their emerging role as potential important mediators of renal failure in general, thus suggesting that they might also contribute to renal dysfunction in the setting of advanced hepatic disease. Most but not all investigators, have demonstrated that circulating ET-1 levels are elevated in patients with advanced liver disease, and some reports have suggested that the magnitude of the elevation correlates with the degree of renal dysfunction. Concomitantly, several investigators have demonstrated NO overproduction as assessed by elevated levels of NO2- and NO3- in patients with advanced liver disease. It has been suggested that serum nitrite/nitrate levels are highest in patients with functional renal failure (i.e., HRS) and that these levels correlate with the magnitude of endotoxemia. Although large voids in our knowledge remain, the available evidence suggest that a reset balance between vasoconstrictor and vasodilatory stimuli may contribute to the renal hemodynamic abnormalities that characterize the renal functional abnormalities of liver disease.