Interleukin-1 and interleukin-6 mediated skeletal muscle arteriolar vasodilation: in vitro versus in vivo studies.
Interleukin-1 and interleukin-6 mediated skeletal muscle arteriolar vasodilation: in vitro versus in vivo studies.
复制标题
Interleukin-1 和 interleukin-6 介导的骨骼肌小动脉血管舒张：体外与体内研究。
DOI：
10.1097/00024382-199803000-00009
复制
发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Hill,MA
中科院分区：
文献类型：
--
作者：
Minghini,A;Britt,LD;Hill,MA
白细胞介素 (IL) 1 和 IL-6 与感染性休克的全身血管阻力降低有关；然而，它们的作用位点和潜在机制仍不清楚。本研究使用体外和体内制剂确定了 IL-1 和 IL-6 对大鼠骨骼肌小动脉的影响。在体外制备中，从大鼠中分离一级提睾小动脉，用微量移液器插管，加压至70mmHg，灌注生理盐水溶液，并在没有管腔内流动的情况下实现自发的基础张力。在体内制备中，通过手术打开麻醉大鼠的提睾肌，将其作为平板固定在光学基座上，并灌注生理盐水溶液。使用透照视频显微镜研究三级小动脉的反应。在两种小动脉制剂中，在细胞因子暴露和冲洗之前和之后评估血管直径和去氧肾上腺素（PE）反应性。体外暴露 IL-1（20 ng/mL（n= 8）或 60 ng/mL（n= 4））或 IL-6（500 U/mL（n= 2）或 1,000 U/mL（n= 4））1 小时不会引起小动脉血管舒张或 PE 反应性变化。然而，在体内暴露IL-1（.01、.1、1.0或20ng/mL）1小时期间，小动脉直径从最大直径（Dmax）的47+/-2%增加到58+/-2%（n=14，p<.0001），从Dmax的45+/-2增加到69+/-3%（n=14，p<.0001），从分别为 Dmax 的 45+/-3 至 96+/-2%（n= 8，p<.0001），以及 Dmax 的 47+/-4 至 96+/-1%（n=14，p<.0001）。细胞因子冲洗导致小动脉恢复到基础直径。细胞因子暴露和清除不影响小动脉PE反应性。体内暴露 IL-6（10、50 或 250 U/mL）1 小时，直径从 Dmax 的 47+/-2% 增加到 57+/-2%（n= 14，p<.0001），从 Dmax 的 46+/-2% 增加到 75+/-3%（n= 14，p<.0001），以及从 Dmax 的 46+/-2% 增加到 68+/-4%（n= 15，p<0001）。 IL-6（10、50 或 250 U/mL）冲洗后，小动脉扩张持续，从 16.3+/- 开始。 5至20.1+/-1.4μm(n＝14，p<.003)，从16.1+/-。 4 至 20.1+/-。 6μm（n=14，p<.0001），并且从17.7+/-。 4 至 22.5+/-。分别为8μm（n=15，p<.0001）。 PE 反应性没有变化。这些数据表明细胞因子IL-1和IL-6是体内条件下骨骼肌阻力血管的有效扩张剂。然而，鉴于在体外分离条件下IL-1和IL-6不能有效引起类似小动脉的松弛，因此表明IL-1和IL-6与实质或血管内因子相互作用以引起小动脉松弛。
Interleukin (IL) 1 and IL-6 have been implicated in the decreased systemic vascular resistance of septic shock; however, their sites of action and underlying mechanisms remain unclear. This study determined the effects of IL-1 and IL-6 on rat skeletal muscle arterioles using both in vitro and in vivo preparations. In the in vitro preparation, first order cremasteric arterioles were isolated from rats, cannulated with micropipettes, pressurized to 70 mmHg, superfused with physiologic saline solution, and allowed to achieve spontaneous basal tone in the absence of intraluminal flow. In the in vivo preparation, the cremaster muscle of anesthetized rats was surgically opened, secured as a flat sheet over an optical pedestal, and superfused with physiologic saline solution. Responses of third order arterioles were studied using transillumination video microscopy. In both arteriolar preparations, vessel diameter and phenylephrine (PE) responsiveness were assessed before and after cytokine exposure and washout. In vitro exposure of IL-1 (20 ng/mL (n= 8) or 60 ng/mL (n= 4)) or IL-6 (500 U/mL (n= 2) or 1,000 U/mL (n= 4)) for 1 h did not cause arteriolar vasodilation or change in PE responsiveness. However, during a 1 h in vivo exposure of IL-1 (. 01,. 1, 1.0, or 20 ng/mL), arteriolar diameter increased from 47+/-2 to 58+/-2% of maximum diameter (Dmax)(n= 14, p<. 0001), from 45+/-2 to 69+/-3% of Dmax (n= 14, p<. 0001), from 45+/-3 to 96+/-2% of Dmax (n= 8, p<. 0001), and from 47+/-4 to 96+/-1% of Dmax (n= 14, p<. 0001), respectively. Cytokine washout resulted in arteriolar return to basal diameter. Cytokine exposure and washout did not affect arteriolar PE responsiveness. In vivo exposure of IL-6 (10, 50, or 250 U/mL) for 1 h increased diameter from 47+/-2 to 57+/-2% of Dmax (n= 14, p<. 0001), from 46+/-2 to 75+/-3% of Dmax (n= 14, p<. 0001), and from 46+/-2 to 68+/-4% of Dmax (n= 15, p<. 0001), respectively. After washout of IL-6 (10, 50, or 250 U/mL), arteriolar dilation persisted, from 16.3+/-. 5 to 20.1+/-1.4 [mu] m (n= 14, p<. 003), from 16.1+/-. 4 to 20.1+/-. 6 [mu] m (n= 14, p<. 0001), and from 17.7+/-. 4 to 22.5+/-. 8 [mu] m (n= 15, p<. 0001), respectively. There was no change in PE responsiveness. These data indicate that the cytokines IL-1 and IL-6 are potent dilating agents for skeletal muscle resistance vessels under in vivo conditions. However, given that IL-1 and IL-6 are ineffective in causing relaxation of similar arterioles under isolated in vitro conditions, it is suggested that IL-1 and IL-6 interact with parenchymal or intravascular factors to elicit arteriolar relaxation.