RESEARCH SUPPORT, NON-U.S. GOV'T
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Role of endogenous carbon monoxide in the pathogenesis of hypotension during septic shock.

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.

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