McIntyre R C, Sheridan B, Agrafojo J, Fullerton D A
Department of Surgery, University of Colorado Health Sciences Center, Denver, USA.
Crit Care Med. 1997 Feb;25(2):318-23. doi: 10.1097/00003246-199702000-00021.
The purpose of this study was to determine the effect of endotoxin on alpha1-adrenergic receptor vasoconstriction and both endothelium-dependent and -independent cyclic guanosine monophosphate (cGMP)-mediated vasodilation in the pulmonary and systemic circulations.
Prospective, multiple group, controlled experimental study.
Medical school research laboratory.
Male Sprague-Dawley rats, weighing 250 to 350 g.
Six hours after endotoxin (20 mg/kg intraperitoneally) or saline, the response to the a) alpha1-adrenergic receptor agonist, phenylephrine; b) endothelium-dependent vasodilator, acetylcholine; and c) the endothelium-independent vasodilator, sodium nitroprusside, was determined in isolated rat pulmonary artery and thoracic aortic rings.
Endotoxin caused a significant decrease in the response to phenylephrine in the aorta but did not affect the response in the pulmonary artery. Endotoxin caused significant impairment of relaxation to acetylcholine and sodium nitroprusside in the pulmonary circulation. In control rings, only 4 +/- 1% of the preconstricted tension remained in response to acetylcholine vs. 77 +/- 3% following endotoxin administration (p < .05). Similarly, sodium nitroprusside resulted in complete pulmonary ring relaxation in controls vs. 18 +/- 3% tension remaining following endotoxin administration (p < .05). On the other hand, only the response to acetylcholine was dysfunctional in the thoracic aorta. In thoracic aortic rings from control rats, acetylcholine caused complete relaxation; however, 23 +/- 5% of the preconstricted tension remained following endotoxin administration. The response to sodium nitroprusside in the thoracic aorta from endotoxin-treated rats was not different from control.
From these data, we conclude that endotoxin causes organ-specific changes in vascular reactivity. These changes in vascular reactivity favor a decrease in vascular pressure and resistance in the systemic circulation, and an increase in vascular pressure and resistance in the pulmonary circulation in response to endotoxin.
本研究旨在确定内毒素对α1 - 肾上腺素能受体介导的血管收缩以及肺循环和体循环中内皮依赖性和非内皮依赖性环磷酸鸟苷（cGMP）介导的血管舒张的影响。
前瞻性、多组、对照实验研究。
医学院研究实验室。
体重250至350克的雄性Sprague - Dawley大鼠。
在内毒素（20毫克/千克腹腔注射）或生理盐水处理6小时后，在离体大鼠肺动脉和胸主动脉环中测定对以下物质的反应：a）α1 - 肾上腺素能受体激动剂去氧肾上腺素；b）内皮依赖性血管舒张剂乙酰胆碱；c）非内皮依赖性血管舒张剂硝普钠。
内毒素导致主动脉对去氧肾上腺素的反应显著降低，但不影响肺动脉的反应。内毒素导致肺循环中对乙酰胆碱和硝普钠的舒张反应显著受损。在对照环中，乙酰胆碱作用后，预收缩张力仅剩余4±1%，而在内毒素给药后为77±3%（p < 0.05）。同样，硝普钠在对照中可使肺环完全舒张，而在内毒素给药后仅剩余18±3%的张力（p < 0.05）。另一方面，仅胸主动脉中对乙酰胆碱的反应功能失调。在对照大鼠的胸主动脉环中，乙酰胆碱可引起完全舒张；然而，在内毒素给药后仍保留23±5%的预收缩张力。内毒素处理大鼠的胸主动脉中对硝普钠的反应与对照无差异。
根据这些数据，我们得出结论，内毒素会引起血管反应性的器官特异性变化。这些血管反应性的变化有利于体循环中血管压力和阻力的降低，以及肺循环中血管压力和阻力因内毒素而增加。
