Acute haemodynamic effects of IL-6 treatment in vivo: Involvement of vagus nerve in NO-mediated negative inotropism
Acute haemodynamic effects of IL-6 treatment in vivo: Involvement of vagus nerve in NO-mediated negative inotropism
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DOI：
10.1016/j.cyto.2005.01.009
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发表时间：
2005-06-07
期刊：
影响因子：
3.8
通讯作者：
Ferrari, R
中科院分区：
文献类型：
--
作者：
Comini, L;Pasini, E;Ferrari, R
白细胞介素-6 （IL-6）降低心肌血流动力学。然而，IL-6作用的内在机制尚不清楚。我们假设由神经元合酶（nNOS）合成的一氧化氮（NO）可能是il -6介导的心脏作用的分子介质。因此，我们在体内研究IL-6急性给药后：(1)NO通路的作用；(2)左心室前表面心内迷走神经节nNOS衍生NO的重要性。SD大鼠（225 ~ 250 g）麻醉（戊巴比妥钠30 mg/kg腹腔注射）并通气。通过四个实验组研究单次IL-6 （100 μ g/kg静脉注射）的作用：(a) IL-6 (n = 6), (b) IL-6加30 mg/kg L-NAME（一种eNOS和nNOS抑制剂，n = 6）， (c) IL-6加25 mg/ka 7-NI（一种特异性nNOS抑制剂，n = 6）， (d) IL-6加迷走神经切除（n = 6）。我们评估了以下参数：平均主动脉压（MAP）、左室末收缩压（LVESP）、左室正峰值dP/dt （PP dP/dt）。数据以平均值+/- sem表示。IL-6导致MAP（-21.8%的基础值，p < 0.05）、LVESP（从130 +/- 4.2降至1056.5 mmHg, p < 0.05）和PP dP/dt（从5390 +/- 158降至4400 +/- 223 mmHg/s， p < 0.02）短暂但显著降低。L-NAME或7-NI联合治疗完全消除了IL-6的作用。迷走神经切除术显著降低了血流动力学的影响（MAP：基础的-10%:p = ns； LVEDS从125 +/- 7.3降至117 +/- 6.8 mmHg, p < 0.05； PP dP/dt从5500 +/- 150降至5000 +/- 143 mmHg/s， p < 0.05）。我们得出结论，急性给药IL-6引起短暂但显著的心脏负性肌力。IL-6血流动力学的影响部分是由位于迷走左室神经节的nNOS合成的NO引起的。(c) 2005 Elsevier Ltd版权所有。
Interleukin-6 (IL-6) reduces myocardial haemodynamics. However, the intrinsic mechanisms of IL-6 effects are not known. We hypothesized that nitric oxide (NO) synthesised by neuronal synthase (nNOS) can be the molecular mediator of IL-6-mediated cardiac effects. Thus, we investigated in vivo after IL-6 acute administration: (1) the role of NO pathway; (2) the importance of NO derived from nNOS located in intracardiac vagal ganglion in the anterior surface of the left ventricle.Sprague-Dawley (SD) rats (225-250 g) were anaesthetized (sodium pentobarbital 30 mg/kg intraperitoneally administered) and ventilated. The effects of a single IL-6 bolus (100 mu g/kg intravenously administered) were studied in four experimental groups: (a) IL-6 (n = 6), (b) IL-6 Plus 30 mg/kg Of L-NAME (an eNOS and nNOS inhibitor; n = 6), (c) IL-6 plus 25 mg/ka of 7-NI (a specific nNOS inhibitor; n = 6) (d) IL-6 plus vagal resection (n = 6).We evaluated the following parameters: mean aortic pressure (MAP), left ventricular end systolic pressure (LVESP), left ventricular positive peak dP/dt (PP dP/dt). Data are expressed as mean +/- sem. IL-6 caused a transient but significant reduction of MAP (-21.8% of basal: p < 0.05), LVESP (from 130 +/- 4.2 to 1056.5 mmHg: p < 0.05) and PP dP/dt (from 5390 +/- 158 to 4400 +/- 223 mmHg/s, p < 0.02). Concomitant treatment with L-NAME or 7-NI totally abolished IL-6 effects. Vagal resection significantly reduced the haemodynamic effects (MAP: -10% of basal: p = ns; LVEDS: from 125 +/- 7.3 to 117 +/- 6.8 mmHg, p < 0.05; PP dP/dt from 5500 +/- 150 to 5000 +/- 143 mmHg/s, p < 0.05).We conclude that acute administration of IL-6 caused transient but significant cardiac negative inotropism. IL-6 haemodynamic effects are partly due to NO synthesised by nNOS located in vagal left ventricular ganglia. (c) 2005 Elsevier Ltd. All rights reserved.