McIntyre R C, Pulido E J, Sheridan B, Meldrum D R, Bensard D D, Fullerton D A
Department of Surgery, University of Colorado Health Sciences Center and The Veterans Affairs Medical Center, Denver 80262, USA.
J Trauma. 1998 Nov;45(5):862-7. doi: 10.1097/00005373-199811000-00003.
The purpose of this study was to determine the effect of endotoxin on vasorelaxation in the pulmonary and systemic circulations in response to the following agonists that require generation of cyclic adenosine monophosphate: (1) beta-adrenergic receptor stimulation with isoproterenol; (2) H2 receptor stimulation with dimaprit; and (3) adenylate cyclase stimulation with forskolin.
Male Sprague-Dawley rats weighing 250 to 350 g were injected with endotoxin (20 mg/kg intraperitoneal) or saline. Six hours later, the cumulative dose response to beta-adrenergic receptor stimulation (isoproterenol), H2 receptor stimulation (dimaprit), and adenylate cyclase stimulation (forskolin) was determined in isolated rat pulmonary artery and thoracic aortic rings preconstricted with phenylephrine.
Endotoxin caused significant impairment of relaxation to isoproterenol in the pulmonary artery, but the response in the aorta was not different from the control response. In the pulmonary circulation, endotoxin converted the response to dimaprit from vasorelaxation to vasoconstriction. On the other hand, dimaprit resulted in vasorelaxation in the thoracic aorta after endotoxin; however, the response was impaired compared with the control response. Endotoxin did not affect the dose response to forskolin in either the pulmonary artery or the thoracic aorta.
From these data, we conclude that endotoxin causes regional specific changes in vascular reactivity. These changes in vascular reactivity result in preserved vasorelaxation in the systemic circulation and impairment of vasorelaxation in the pulmonary circulation in response to endotoxin.
本研究旨在确定内毒素对肺循环和体循环血管舒张的影响，以应对以下需要生成环磷酸腺苷的激动剂：（1）用异丙肾上腺素刺激β-肾上腺素能受体；（2）用二甲双胍刺激H2受体；（3）用福司可林刺激腺苷酸环化酶。
给体重250至350克的雄性Sprague-Dawley大鼠注射内毒素（20毫克/千克腹腔注射）或生理盐水。6小时后，在预先用去氧肾上腺素收缩的离体大鼠肺动脉和胸主动脉环中，测定对β-肾上腺素能受体刺激（异丙肾上腺素）、H2受体刺激（二甲双胍）和腺苷酸环化酶刺激（福司可林）的累积剂量反应。
内毒素导致肺动脉对异丙肾上腺素的舒张功能显著受损，但主动脉的反应与对照反应无差异。在肺循环中，内毒素使对二甲双胍的反应从血管舒张转变为血管收缩。另一方面，二甲双胍在内毒素作用后导致胸主动脉血管舒张；然而，与对照反应相比，该反应受损。内毒素对肺动脉或胸主动脉中福司可林的剂量反应均无影响。
根据这些数据，我们得出结论，内毒素会引起血管反应性的区域特异性变化。这些血管反应性的变化导致体循环中血管舒张得以保留，而肺循环中血管舒张对内毒素的反应受损。
