Chronic alcohol consumption increases heme oxygenase-1 (HO-1) induction following hemorrhagic shock

Chronic alcohol consumption increases hepatic constrictor response to endothelin and exacerbates microvascular injury following hemorrhage. To test whether this might be due in part to altered induction of stress-induced dilators we determined the levels of expression of HO-1 and inducible nitric oxide synthase (NOS) which produce CO and NO respectively Rats were maintained on chronic alcohol (Lieber-DeCarli diet; ALC) or control(C) diet for 5 wks and then subjected to hemorrhagic shock (45 min) and resuscitation (HS/R) for 1, 6, or 24 hours. Prior to HS/R, there was a slightly elevated HO-1 in ALC as indicated by both Northern and Western blot. There was no detectable iNOS. During resuscitation, HO-1 mRNA and protein were markedly induced in both ALC and C. HO-1 mRNA levels were increased to a peak of 50±11 ( C ) and 70±13 (ALC) fold at 1 hr of HS/R and the increase was more prolonged in ALC (at 24 hr: C-2.1±.4x; ALC-6.2±1.5x). At later time points higher levels of HO-1 induction were associated with development of injury. At 24 hr, HO-1 mRNA in livers from rats with pericentral necrosis were elevated 5.3×( C) and 8.2×(ALC) compared to 1.7×( C) and 2.1× (ALC) without injury. In contrast to the marked HO-1 induction, there was no consistently observed induction of iNOS in any group. These results indicate that HO-1 but not iNOS may act as a significant stress-induced source of endogenous dilators in HS/R to balance upregulated constrictors such as endothelin. The increased induction following chronic alcohol is likely a response to increased injury. Supp by Ale Bev Med Res Found.