Rosenberg R B, Broner C W, O'Dorisio M S
Department of Pediatrics, Ohio State University, Children's Hospital, Columbus.
Biochem Med Metab Biol. 1994 Apr;51(2):149-55. doi: 10.1006/bmmb.1994.1019.
Endotoxin and other bacterial products induce the release of mediators which alter the circulation and cellular metabolism. Recent evidence suggests nitric oxide (NO) is one such mediator. The proposed mechanism by which NO produces hypotension is the activation of guanylate cyclase with subsequent biosynthesis of 3':5' cyclic guanosine monophosphate (cGMP). We studied the production of cGMP during Escherichia coli-induced septic shock in two experiments; the first with sepsis alone and the second using NG-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of nitric oxide synthase. Animals in both experiments experienced significant bacteremia (P < 0.05), endotoxemia (P < 0.05), and lactic acidosis (P < 0.03). Mean arterial blood pressure decreased (P < 0.03) and heart rate increased (P < 0.05) within both groups but did not differ between groups. A significant increase in the production of circulating whole blood cGMP occurred at 3-5 h (P < 0.03). There was significantly less cGMP produced by the L-NMMA-treated animals (P < 0.01). These results demonstrate an elevation in cGMP during septic shock which is attenuated by the addition of L-NMMA. This suggests that NO may be present during gram-negative septic shock and its effects mediated through cGMP.
内毒素及其他细菌产物可诱导介质释放，这些介质会改变循环及细胞代谢。最近的证据表明一氧化氮（NO）就是这样一种介质。NO导致低血压的推测机制是激活鸟苷酸环化酶，随后生物合成3':5'环磷酸鸟苷（cGMP）。我们在两项实验中研究了大肠杆菌诱导的脓毒症休克期间cGMP的产生；第一项实验仅观察脓毒症，第二项实验使用一氧化氮合酶的竞争性抑制剂NG-单甲基-L-精氨酸（L-NMMA）。两项实验中的动物均出现显著菌血症（P < 0.05）、内毒素血症（P < 0.05）和乳酸性酸中毒（P < 0.03）。两组动物的平均动脉血压均下降（P < 0.03），心率均增加（P < 0.05），但两组之间无差异。循环全血cGMP的产生在3 - 5小时显著增加（P < 0.03）。L-NMMA处理的动物产生的cGMP显著减少（P < 0.01）。这些结果表明脓毒症休克期间cGMP升高，而添加L-NMMA可使其减弱。这表明在革兰氏阴性脓毒症休克期间可能存在NO，其作用通过cGMP介导。
