Abstract
Both the production of nitric oxide (NO) through the inducible NO synthase (iNOS) pathway and the production of carbon monoxide (CO) through the inducible heme oxygenase (HO-1) pathway have been implicated as major contributors in the process of endotoxin shock. It is proposed that there is a reciprocal action between NO and CO, because both of them bind to heme moiety of guanylyl cyclase to produce cGMP during endotoxin shock. Using a rat endotoxin shock model, the effects of iNOS inhibitor (L-canavanine, CAN) and HO inhibitor (zinc protoporphyrin, ZPP) on the blood concentration of nitrosyl hemoglobin (NO-Hb) and carboxy-hemoglobin (CO-Hb) were studied. CAN attenuated the endotoxin-induced hypotension and only inhibited the increase in NO-Hb. ZPP also abrogated hypotension, but only inhibited the increase in CO-Hb. These data suggest that both inhibition of iNOS pathway and HO-1 pathway are useful for the treatment of hypotension. However, both pathways work on the vascular smooth muscle independently during endotoxin shock.
