Effects of endogenous carbon monoxide/nitric oxide on cholecystokinin octapeptide reversed vascular hyporeactivity in endotoxemic rats / 中国病理生理杂志

ABSTRACT

AIM: To explore the effects of cellular signal transduction pathways of heme oxygenase-1(HO-1)-carbon monoxide (CO)-cyclic GMP (cGMP) and nitric oxide synthase (NOS)-nitric oxide (NO)-cGMP on cholecystokinin octapeptide (CCK-8) reversed vascular hyporeactivity in endotoxemic rats. METHODS: According to the treatments given in vivo , rats were devided into four groups: control; lipopolysaccharide (LPS); CCK and CCK+LPS. Using isolated vascular ring tension detecting technique, thoracic aortic rings (TARs) were prepared and accumulation of contractive responses to phenylephrine (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), L-arginine (L-Arg, substrate of NOS), aminoguanidine (AG, selective inhibitor of iNOS), N ?-nitro-L-arginine (L-NNA, inhibitor of NOS) or methylene blue (MB, inhibitor of guanylyl cyclase), respectively. RESULTS: CCK-8 alone did not affect vascular tension. Injection of LPS induced the hyporeactivity of the TARs and was reversed by pretreatment of CCK-8. In LPS and CCK+LPS groups, the hyporeactivity was partly reversed by incubation of TARs with ZnPP-IX or AG, and restored to normal by incubation of TARs with L-NNA or MB. Incubation of TARs with He or L-Arg showed to make the vascular hyporeactivity worse in different degree. CONCLUSIONS: CCK-8 alone did not affect the activity of HO-1 and iNOS but influenced the activity of these enzymes induced by LPS, which lead to reduced CO/NO production, decreased the content of cGMP and plays its important role in reversing vascular hyporeactivity in endotoxemic rats.