RELATIONSHIP BETWEEN NITRIC OXIDE AND CARBONMONOXIDE DURING SHOCK AND ITS CONTROL

采用大鼠内毒素休克模型，研究了诱导型一氧化氮（iNOS）抑制剂（L-刀豆氨酸，CAN）和血红素加氧酶（HO）抑制剂（锌原卟啉，ZPP）对血中亚硝基血红蛋白（NO-Hb）和碳氧血红蛋白（CO-Hb）浓度的影响。CAN可减轻内毒素引起的低血压，仅抑制NO-Hb的升高。ZPP也消除低血压，但仅抑制CO-Hb的增加。CAN和ZPP分别独立抑制逆转录聚合酶链反应检测到的iNOS mRNA和HO-1 mRNA的产生。这些数据表明，抑制iNOS通路和HO-1通路均有助于治疗低血压，但在内毒素休克期间，这两条通路均独立地作用于血管平滑肌。在工作大鼠心脏模型中，iNOS抑制剂而非非特异性NOS抑制剂减轻炎性细胞因子诱导的心脏抑制。在大鼠血管环模型中，iNOS抑制剂而非非特异性NOS抑制剂减轻炎性细胞因子诱导的血管低反应性。这些数据表明，在休克过程中的循环保护作用的组成型NOS。

Using a rat endotoxin shock model, the effects of inducible nitric oxide (iNOS) inhibitor (L-canavanine, CAN) and hemeoxygenase (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. The increases in production of iNOS mRNA and HO-1 mRNA detected by reverse transcription-polymerase chain reaction were inhibited by CAN and ZPP, respectively and independently. 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. In a working rat heart model, iNOS inhibitor but not non-specific NOS inhibitor attenuated cardiac depression induced by inflammatory cytokines. In a rat vascular ring model, iNOS inhibitor but not non-specific NOS inhibitor attenuated vascular hyporeactivity induced by inflammatory cytokines. These data suggest the circulatory protective role of constitutive NOS during shock.