Nitric oxide synthase and heme oxygenase expressions in human liver cirrhosis.

AIM

Portal hypertension is a common complication of liver cirrhosis. Intrahepatic pressure can be elevated in several ways. Abnormal architecture affecting the vasculature, an increase in vasoconstrictors and increased circulation from the splanchnic viscera into the portal system may all contribute. It follows that endogenous vasodilators may be able to alleviate the hypertension. We therefore aimed to investigate the levels of endogenous vasodilators, nitric oxide (NO) and carbon monoxide (CO) through the expression of nitric oxide synthase (NOS) and heme oxygenase (HO).

METHOD

Cirrhotic (n=20) and non-cirrhotic (n=20) livers were obtained from patients who had undergone surgery. The mRNA and protein expressions of the various isoforms of NOS and HO were examined using competitive PCR, Western Blot and immunohistochemistry.

RESULTS

There was no significant change in either inducible NOS (iNOS) or neuronal NOS (nNOS) expressions while endothelial NOS (eNOS) was up-regulated in cirrhotic livers. Concomitantly, caveolin-1, an established down-regulator of eNOS, was up-regulated. Inducible HO-1 and constitutive HO-2 were found to show increased expression in cirrhotic livers albeit in different localizations.

CONCLUSION

The differences of NOS expression might be due to their differing roles in maintaining liver homeostasis and/or involvement in the pathology of cirrhosis. Sheer stress within the hypertensive liver may induce increased expression of eNOS. In turn, caveolin-1 is also increased. Whether this serves as a defense mechanism against further cirrhosis or is a consequence of cirrhosis, is yet unknown. The elevated expression of HO-1 and HO-2 suggest that CO may compensate in its role as a vasodilator albeit weakly. It is possible that CO and NO have parallel or coordinated functions within the liver and may work antagonistically in the pathophysiology of portal hypertension.