THE ROLE OF NITRIC-OXIDE IN PORTAL HYPERTENSIVE SYSTEMIC AND PORTAL VASCULAR PATHOLOGY

Hypotension, low systemic vascular resistance and reduced sensitivity to vasoconstrictors are features of hyperdynamic syndrome in portal hy pertension (PH) and are pathogenetic factors triggering most serious c linical complications of liver cirrhosis. Nitric oxide (NO) is a power ful vasodilating agent, released from vascular endothelium cell and ef fecting relaxation of vascular smooth muscle. An increased release of NO has been proposed to play a role in the pathogenesis of vasodilatio n and vascular hypocontractility associated with FH. In agreement with this hypothesis, the whole-body production of NO has been found to he increased in PH, and the measurement of NOS mRNA expression in differ ent organs suggest that the splanchnic vascular system is a major sour ce of NO release, Consequently, NO could play a role in the developmen t of the splanchnic hyperaemia, collateral circulation and portal hype rtensive gastropathy. Furthermore, increased generation of NO In centr al circulation likely accounts for pulmonary vasorelaxation and cardia c dysfunction found in cirrhosis. By contrast, PH-associated endotheli al dysfunction seems to invalidate the capability of intrahepatic and intrarenal vasculature to produce NO. A deficient MO release in these vascular territories might contribute to enhancement of PH and develop ment of the hepatorenal syndrome, Overall NO hyperproduction is either the cause (induction of iNOS) or the consequence (stimulation of ecNO S) of the hyperdynamic syndrome. This incertitude results from the vet undefined significance of mild and transitory activation of the endot oxin-cytokines axis for iNOS induction and contradictory data on speci fic iNOS and ecNOS activities. A contribution of each isoform of NOS t o pathogenesis of the hyperdynamic syndrome probably depends on the mo del of PH in animal studies and the aetiology or severity of cirrhosis in human studies.