Plasma endothelin in patients with endotoxemia and dynamic comparison between vasoconstrictor and vasodilator in cirrhotic patients

Abstract

Key Words: hypertension, portal; liver cirrhosis; portosystemic shunt, surgical; endothelins; radioimmunoassay; epoprostenol; liver cirrhosis

INTRODUCTION

Portal hypertension is a common clinical syndrome characterized by an abnormal increase in portal blood to the systemic circulation, bypassing the liver. Recent studies have reported that humoral substances play an important role in the pathogenesis of portal hypertension, either by increasing vascular resistance at both the intrahepatic and porto-collateral sites or affecting splanchnic vasodilation with a concomitant increase in parto-collateral blood flow[1-6].

Endothelin (ET) released by endothelial cells is a 21-amino acid peptide with potent vasoconstrictor action. Endothelin comprises a family of four homologous isopeptides in human and animals (ET-1, ET-2, and ET-3, VIC)[7-14]. Most reported data are related to ET-1, which is the most powerful vasoconstrictor. Owing to a variety of reasons, reports concerning endothelin levels in cirrhotics are not consistent with each other. Endothelin concentrations in plasma have been reported to be increased in some studies and normal or reduced in others[15-20]. Present evidence suggests that endothelin may play an important role in modulating intrahepatic vascular resistance[21-24]. However, the relationship between vasoconstrictor (ET, TX-) and vasodilator (PGI₂) during portosystemic shunt has not been documented.

METHODS

We measured the concentration of endothelin in plasma using radioimmunoassay in 121 patients with cirrhosis and compared these values with 50 age- and sex-matched control subjects, and evaluated systemic endotoxemia. At the same time, perioperative plasma vasoconstrictor and vasodilator were clinically observed in 30 portohypertensive cirrhotic patients undergoing portosystemic shunt.

RESULTS

Plasma endothelin levels were higher in cirrhotic patients with ascites than in those without ascites. Femoral venous plasma endothelin levels averaged 90 ± 23 ng/L in cirrhotic patients versus 34 ± 8 ng/L in controls (P = 0.000), and that of cirrhotics with ascites was higher than those without 106 ± 17 ng/L vs 90 ± 23 ng/L (P = 0.002). Moreover, plasma endothelin levels increased in proportion to the severity of endotoxemia (r_s = 0.61, P = 0.034). Both the levels of plasma vasoconstrictors (ET, TX-) and of the vasodilator (PGI₂) were higher in portohypertensive cirrhotic patients (ET: 107.8 ± 25.9 ng/L vs 48.1 ± 9.4 (P = 0.000); TX-: 349.7 ± 198.4 ng/L vs 156.3 ± 54 (P = 0.000); PGI₂: 463.1 ± 108.3 ng/L vs 227.2 ± 46 (P = 0.000), and their concentrations decreased significantly in patients after portosystemic shunt (P = 0.002).

DISCUSSION

These results suggest that endothelin has significant influence on the portal vascular resistance of cirrhotic liver in vivo and may play an important role in the pathogenesis of portal hypertension[25-28]. Endotoxin may lead to the increased synthesis and release of endothelin. It could be that a dynamic balance between levels of vasoconstrictor and vasodilator in plasma exists in the pathophysiology of portohypertensive cirrhotic patients after portosystemic shunt.