AIMTo explore the effects of heme- heme oxygenase-1 (HO-1)-carbon monoxide(CO)-cyclic GMP (cGMP)on aortic vascular reactivity in endotoxemic rats and its molecular mechanism.

METHODSBy using isolated vascular ring tension detecting technique, cumulative responses of thoracic aortic rings (TARs)to phenylephrine (PE) were measured at 6 h after lipopolysaccharide administration. Effects on contractile responses to PE were measured under which the TARs were incubated with hemin (He, donor of CO), zinc-protoporphyrin-IX(ZnPP-IX, selective inhibitor of HO-1), or methylene blue (MB, inhibitor of guanylyl cyclase), respectively. The content of CO and the activity of HO-1 were measured. The protein and the gene expression of HO-1 were examined by Western blot and RT-PCR.

RESULTSContractile responses of TARs to cumulative doses of PE were depressed by pretreated with LPS. The hyporesponsiveness was partly reversed by incubation with ZnPP-IX and was restored to normal by incubation with MB in endotoxemic rats. Incubation with He could contribute to the vascular hyporeactivity. The content of CO, the activity and the protein and the gene expression of HO-1 were significantly increased in aorta of endotoxemic rats.

CONCLUSIONLPS could induce the HO-1 mRNA and the protein expression, the activity of HO-1 increase in aorta, lead to active the pathway of heme-HO-1-CO-cGMP, which is one of the important mechanisms of the vascular hyporeactivity in endotoxemic rats.