The present study investigated the contribution of endogenous heme oxygenase (HO)/carbon monoxide (CO) system to hypertension pathogenesis of rats. Zinc deuteroporphyrin 2,4-bisglycol (ZnDPBG),an inhibitor of heme oxygenase (HO), was used to inhibit HO activity in vivo. It was found that the blood pressure of rats with HO inhibition was significantly elevated, and plasma levels of adrenaline, noradrenaline,endothelin, nitrate and nitrite were significantly increased. HO activity and HbCO formation within vascular smooth muscle tissues were significantly inhibited after administration of ZnDPBG. Furthermore, administration of exogenous CO into HO inhibiting rats led to MABP decrease, but injection of HO substrate, heme-Llysinate, had no effect on HO inhibition-induced hypertension. In spontaneously hypertensive rats, injection of exogenous CO resulted in a significant decrease of MABP, and heme-L-lystnate had a similar effect with exogenous CO. These data show that HO/CO system has an anti-hypertension biological action, suggesting that endogenous CO plays an important role in hypertension pathogenesis.

A sepsis model induced by cecal ligation and puncture was used to study the role of endogenous carbon monoxide in hypotension pathogenesis of rats during septic shock. After administration of zinc deuteroporphyrin 2,4-bisglycol (ZnDPBG),an inhibitor of heme oxygenase (HO),blood pressure (BP),HO activity and carbon monoxide (CO) release from vascular muscle tissue were measured. The results showed that BP of sepsis rats,including systolic and diastolic arterial BP,decreased significantly while HO activity and CO content were significantly increased. In contrast,after administration of ZnDPBG,BP of sepsis rats was significantly increased while the HO activity and CO production were significantly decreased. These findings suggest that HO activity and CO release within vascular musculature are increased during septic shock;inhibition of HO may elevate BP of rats during septic shock through a decrease of endogenous CO production. It is concluded that endogenous CO derived from vascular muscle cells plays an important role in regulating vascular tone,and the up-regulation of HO activity followed by subsequent CO production contributes to hypotension pathogenesis during septic shock.