RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR REVERTS VASCULAR DYSFUNCTION

The aim of our study was to investigate the vascular effects of recomb inant human granulocyte colony-stimulating factor (rh G-CSF) in a rat model of irreversible vascular failure, Male anesthetized rats were su bjected to the clamping of the splanchnic arteries for 45 min. This su rgical procedure resulted in an irreversible state of shock (splanchni c artery occlusion shock) characterized by high mortality rate (0% sur vival, 120 min following the release of clamps), a profound hypertensi on and vascular dysfunction consisting of a marked hyporeactivity to p henylephrine (PE 1 nM-10 mu M) of aortic rings, Administration of reco mbinant human granulocyte colony-stimulating factor (20 mu g/kg i.v, 5 min after the release of occlusion) increased survival rate (90% 4 h after the release of occlusion), blunted the profound hypotension and reverted the marked vascular dysfunction, Finally, rh G-CF inhibited t he activity of inducible nitric oxide synthase in peritoneal macrophag es activated with endotoxin. Our data suggest that rh G-CSF may influe nce vascular function when low-flow states occur.