Evora P R, Ekin S, Pearson P J, Schaff H V
Section of Cardiovascular Surgery, Mayo Clinic, Rochester, MN, USA.
Braz J Med Biol Res. 1998 Oct;31(10):1329-34. doi: 10.1590/s0100-879x1998001000014.
Early systemic arterial hypotension is a common clinical feature of Pseudomonas septicemia. To determine if Pseudomonas aeruginosa endotoxin induces the release of endothelium-derived nitric oxide (EDNO), an endogenous nitrovasodilator, segments of canine femoral, renal, hepatic, superior mesenteric, and left circumflex coronary arteries were suspended in organ chambers (physiological salt solution, 95% O2/5% CO2, pH 7.4, 37 degrees C) to measure isometric force. In arterial segments contracted with 2 microM prostaglandin F2 alpha, Pseudomonas endotoxin (lipopolysaccharide (LPS) serotype 10(Habs) from Pseudomonas aeruginosa (0.05 to 0.50 mg/ml) induced concentration-dependent relaxation of segments with endothelium (P < 0.05) but no significant change in tension of arteries without endothelium. Endothelium-dependent relaxation in response to Pseudomonas LPS occurred in the presence of 1 microM indomethacin, but could be blocked in the coronary artery with 10 microM NG-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of nitric oxide synthesis from L-arginine. The inhibitory effect of L-NMMA on LPS-mediated vasorelaxation of the coronary artery could be reversed by exogenous 100 microM L-arginine but not by 100 microM D-arginine. These experiments indicate that Pseudomonas endotoxin induces synthesis of nitric oxide from L-arginine by the vascular endothelium. LPS-mediated production of EDNO by the endothelium, possibly through the action of constitutive nitric oxide synthase (NOSc), may decrease systemic vascular resistance and may be the mechanism of early hypotension characteristic of Pseudomonas septicemia.
早期系统性动脉低血压是铜绿假单胞菌败血症常见的临床特征。为了确定铜绿假单胞菌内毒素是否能诱导内皮源性一氧化氮（EDNO，一种内源性血管舒张剂）的释放，将犬股动脉、肾动脉、肝动脉、肠系膜上动脉和左旋冠状动脉节段置于器官浴槽中（生理盐溶液，95% O₂/5% CO₂，pH 7.4，37℃）以测量等长力。在使用2微摩尔前列腺素F2α收缩的动脉节段中，铜绿假单胞菌内毒素（来自铜绿假单胞菌的脂多糖（LPS）血清型10（Habs），0.05至0.50毫克/毫升）可诱导有内皮的节段出现浓度依赖性舒张（P < 0.05），但对无内皮的动脉张力无显著影响。在存在1微摩尔吲哚美辛的情况下，对铜绿假单胞菌LPS会出现内皮依赖性舒张，但在冠状动脉中可被10微摩尔NG-单甲基-L-精氨酸（L-NMMA，一种从L-精氨酸合成一氧化氮的竞争性抑制剂）阻断。L-NMMA对冠状动脉LPS介导的血管舒张的抑制作用可被外源性100微摩尔L-精氨酸逆转，但不能被100微摩尔D-精氨酸逆转。这些实验表明，铜绿假单胞菌内毒素可诱导血管内皮从L-精氨酸合成一氧化氮。内皮通过组成型一氧化氮合酶（NOSc）的作用介导LPS产生EDNO，这可能会降低全身血管阻力，并且可能是铜绿假单胞菌败血症早期低血压的机制。
