LIVER SINUSOIDAL ENDOTHELIAL-CELLS ARE RESPONSIBLE FOR NITRIC-OXIDE MODULATION OF RESISTANCE IN THE HEPATIC SINUSOIDS

The mechanisms that regulate vascular resistance in the liver are an a rea of active investigation, Previously, we have shown that nitric oxi de (NO) modulates hepatic vascular tone in the normal rat liver, In th is study, the production of NO is examined in further detail by isolat ing sinusoidal endothelial cells (SEC) from the rat liver, Endothelial NO synthase (eNOS) was present in SEC based on Western blotting and c onfocal immunofluorescence microscopy, Exposure of SEC to flow increas ed the release of NO, To investigate the relevance of these in vitro f indings to the intact liver: we modified an in situ perfusion system t o allow for direct measurement of NO release from the hepatic vasculat ure. NO was released from the hepatic vasculature in a time-dependent manner, and administration of N-monomethyl-L-arginine reduced NO relea se and increased portal pressure, Immunostaining of intact liver demon strated eNOS localization to endothelial cells lining the hepatic sinu soids, These findings demonstrate that SEC in vitro and in vivo expres s eNOS and produce NO basally, and increase their production in respon se to flow, Additionally, an increase in portal pressure concomitant w ith the blockade of NO release directly demonstrates that endogenous e ndothelial-derived NO modulates portal pressure.