Mclntyre R C, Sheridan B, Agrafojo J, Fullerton D A
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262, USA.
Shock. 1997 Jan;7(1):36-41. doi: 10.1097/00024382-199701000-00004.
We hypothesized that pulmonary vasorelaxation mediated by receptors that require generation of cyclic adenosine monophosphate (cAMP) is impaired in endotoxin-induced acute lung injury. The purpose of this study was to determine the effect of endotoxin on the following pathways of pulmonary vasorelaxation that require the generation of cAMP: 1) beta-adrenoreceptor stimulation (response to isoproterenol, ISO), 2) P2 purinoreceptor stimulation (response to adenosine diphosphate, ADP), 3) H2-histamine receptor stimulation (response to dimaprit), 4) adenosine A2 receptor stimulation (response to adenosine, ADO), 5) type 2 E prostaglandin (EP2) receptor stimulation (response to prostaglandin E1, PGE1), and 6) direct adenylate cyclase stimulation (response to forskolin, FSK). We used isolated pulmonary artery rings harvested from rats injected with endotoxin or saline. We found that endotoxin impaired the response to beta-adrenoreceptor stimulation (ISO) and P2 purinoreceptor stimulation (ADP). Endotoxin converted the vasorelaxant effect of H2-histamine receptor stimulation (dimaprit) to vasoconstriction. On the other hand, the response to A2 receptor stimulation (ADO) and EP2 receptor stimulation (PGE1), was normal. The dose response to direct adenylate cyclase stimulation (FSK) was the same as control except at a single concentration (10(-7) M). These data suggest that endotoxin causes selective impairment of pulmonary vasorelaxation through receptors coupled to cAMP generation. This impaired pulmonary vasorelaxation may contribute to the increased pulmonary vascular resistance seen in acute lung injury. These data may lead to therapy that will prevent or improve the pathophysiologic pulmonary circulation in acute lung injury.
我们假设，在内毒素诱导的急性肺损伤中，由需要生成环磷酸腺苷（cAMP）的受体介导的肺血管舒张功能受损。本研究的目的是确定内毒素对以下需要生成cAMP的肺血管舒张途径的影响：1）β-肾上腺素能受体刺激（对异丙肾上腺素的反应，ISO），2）P2嘌呤能受体刺激（对二磷酸腺苷的反应，ADP），3）H2组胺受体刺激（对二甲双胍的反应），4）腺苷A2受体刺激（对腺苷的反应，ADO），5）2型前列腺素E（EP2）受体刺激（对前列腺素E1的反应，PGE1），以及6）直接腺苷酸环化酶刺激（对福斯高林的反应，FSK）。我们使用了从注射内毒素或生理盐水的大鼠身上获取的离体肺动脉环。我们发现内毒素损害了对β-肾上腺素能受体刺激（ISO）和P2嘌呤能受体刺激（ADP）的反应。内毒素将H2组胺受体刺激（二甲双胍）的血管舒张作用转化为血管收缩。另一方面，对A2受体刺激（ADO）和EP2受体刺激（PGE1）的反应是正常的。除了单一浓度（10^-7 M）外，对直接腺苷酸环化酶刺激（FSK）的剂量反应与对照组相同。这些数据表明，内毒素通过与cAMP生成偶联的受体导致肺血管舒张的选择性损害。这种受损的肺血管舒张可能导致急性肺损伤中肺血管阻力增加。这些数据可能会带来预防或改善急性肺损伤中病理生理肺循环的治疗方法。
