Regional haemodynamic responses to infusion of lipopolysaccharide in conscious rats: effects of pre- or post-treatment with glibenclamide
Regional haemodynamic responses to infusion of lipopolysaccharide in conscious rats: effects of pre- or post-treatment with glibenclamide
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DOI：
10.1038/sj.bjp.0702985
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发表时间：
1999-12-01
影响因子：
7.3
通讯作者：
Bennett, T
中科院分区：
文献类型：
--
作者：
Gardiner, SM;Kemp, PA;Bennett, T
1确定K-ATP通道对内毒素血症血流动力学后遗症的假定贡献。在不同的清醒的、长期使用仪器的、不受约束的雄性LongEvans大鼠组中进行了三个实验。在第一个实验中，用K-ATP通道拮抗剂格列本脲预处理，消除了初始的低血压，但没有消除由LPS输注引起的肾血管舒张。然而，随后，在存在格列本脲和LPS的情况下，平均动脉血压显著升高，心动过缓，与在存在溶媒和LPS的情况下观察到的平均动脉血压下降和心动过速形成对比。在格列本脲和LPS存在下的加压和心动过缓变化伴随着后躯流量和血管传导性的显著降低，并且这些显著大于在溶剂和LPS或格列本脲和盐水存在下观察到的。3在盐水和LPS输注开始后6小时给予格列本脲，或在AT（1）-受体拮抗剂氯沙坦和ETA-、ETB-受体拮抗剂SE 209670存在下，在地塞米松不存在或存在下，盐水和LPS输注开始后6小时，导致平均动脉血压显著升高，肾脏、肠系膜和后肢电导降低，尽管后者是唯一一个血流减少的血管床。4结果与K-ATP的贡献一致。通道的LPS引起的血管舒张，特别是在后躯血管床。
1 To determine the putative contribution of K-ATP-channels to the haemodynamic sequelae of endotoxaemia. three experiments were carried out in different groups of conscious, chronically-instrumented, unrestrained, male Long Evans rats.2 Tn the first experiment, pretreatment with the K-ATP-channel antagonist, glibenclamide, abolished the initial hypotension, but not the renal vasodilatation caused by LPS infusion. Subsequently, however, in the presence of glibenclamide and LPS there was a significant increase in mean arterial blood pressure, and a bradycardia, in contrast to the fall in mean arterial blood pressure and the tachycardia seen in the presence of vehicle and LPS. The presser and bradycardic changes in the presence of glibenclamide and LPS were accompanied by significant reductions in hindquarters flow and vascular conductance, and these were significantly greater than those seen in the presence of vehicle and LPS, or glibenclamide and saline.3 Administration of glibenclamide 6 h after the onset of saline and LPS infusion, or 6 h after the onset of saline and LPS infusion in the presence of the AT(1)-receptor antagonist, losartan, and the ETA-, ETB- receptor antagonist, SE 209670, in the absence or presence of dexamethasone, caused a significant increase in mean arterial blood pressure and reductions in renal, mesenteric and hindquarters conductances, although the latter was the only vascular bed in which there was a reduction in flow.4 The results are consistent with a contribution from K-ATP-channels to the vasodilatation caused by LPS, particularly in the hindquarters vascular bed.