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.
|Original language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology