Objective To investigate the regulatory roles and changes of M3 receptor subtype in lipopolysaccharide (LPS)-preincubated rabbit pulmonary arteries, and assess the mechanism of altered vascular reactivity in septic shock.
Methods Pulmonary arteries with intact endothelium were isolated from 26 male New ealand white rabbits weighing 2.0 to 2.5kg. he isolated pulmonary arteries were randomized into two grouops, including a normal group with normal saline and darifenacin adminstration, and an endotoxin group with LPS-preincubation and darifenacin adminstration.he response of arteries to phenylephrine (100μmol/L) and acetylcholine(ACH)(1μmol/L, 10μmol/L, 100μmol/L)were measured in normal and darifenacin-preincubated circumstances.
Results The percentages of ralaxation to ACH (1μmol/L, 10μmol/L, 100μmol/L) were (0.095±0.034)%, (0.150±0.036)%, and (0.445±0.090)% in the normal group, and (0.044±0.016)%, (0.093±0.029)%, (0.311±0.028)% in the endotoxin (LPS 4μg/mL, 4h) group. After pretreatment with M3 receptor antagonist darifenacin on different concentrations, the EC50 values responding to ACH (1μmol/L, 10μmol/L, 100μmol/L) were 1.483, 2.757, 2.958 in the normal group, and 6.015, 6.242, 6.411 in the endotoxin group. After pretreatment with M3 receptor antagonist darifenacin on different concentrations, the inherent activity of a value to ACH (1μmol/L, 10μmol/L, 100μmol/L) were 0.0146, 0.0323, 0.0825 in the normal group, and 0.0124, 0.0245, 0.0556 in the endotoxin group.
Conclusions LPS pre-incubation can reduce the relaxation response to ACH, and M3 receptor subtypes mediated this relaxation response. LPS also reduce the M3 receptor subtype intrinsic activity, which may be one of the mechanisms of decreased relaxation response to ACH in pulmonary arteris after LPS pretreatment, and also one of the mechanisms of pulmonary hypertension in septic shock.
Citation:
Suo Liangyuan, Yu Hongbo, Zhang Jin. Endotoxin Decreases the Relaxation Response to Acetylcholine Mediated by M3 Receptor Subtype in Isolated Rabbit Pulmonary Arteries. Chinese Journal of Respiratory and Critical Care Medicine, 2016, 15(5): 506-510. doi: 10.7507/1671-6205.2016116
Copy
Copyright © the editorial department of Chinese Journal of Respiratory and Critical Care Medicine of West China Medical Publisher. All rights reserved
1. |
尹文, 李俊杰.感染性休克发病机制的研究进展.中国急救医学, 2015, 35:196-201.
|
2. |
Sheridan B C, Mcintyre R Jr, Moore E E, et al.Neutrophils mediate pulmonary vasomotor dysfunction in endotoxin-induced acute lung injury.J Trauma, 1997, 42:391-396.
|
3. |
Attinà TM, Oliver JJ, Malatino LS, et al. Contribution of the M3 muscarinic receptors to the vasodilator response to acetylcholine in the human forearm vascular bed.Br J Clin Pharmacol, 2008, 66:300-303.
|
4. |
黄新莉, 周晓红, 韦鹏, 等.内源性硫化氢在脂多糖引起的肺动脉高压中的作用.生理学报, 2008, 60:211-215.
|
5. |
齐小非, 张锦.感染性休克时肺动脉改变及调节机制的研究进展.中国危重病急救医学, 2008, 20:630-633.
|
6. |
索良源, 张锦.去甲肾上腺素治疗感染性休克时对肺动、静脉血管压力的影响.中国呼吸与危重监护杂志, 2014, 13:508-512.
|
7. |
佟冬怡, 张锦, 于泓波, 等.去甲肾上腺素和多巴胺对内毒素孵育兔肺动脉和体动脉环张力影响的比较.中国呼吸与危重监护杂志, 2010, 9:188-192.
|
8. |
章静, 史佳, 余剑波, 等.P13K/Akt/Nrf2信号通路在兔内毒素休克诱发急性肺损伤中的作用.中华麻醉学杂志, 2015, 35:1257-1260.
|
9. |
Frostermann U, Pollock JS, Nakane M, et al. Noitric oxide synthases in the cardiovascular system. Trends Cardiovasc Med, 1993, 3:104-110.
|
10. |
佟冬怡, 于泓波, 李娜, 等.预注不同剂量长托宁对内毒素休克兔肺动脉张力的影响及机制探讨.中国医科大学学报, 2011, 40:228-240.
|
11. |
Stojnic N, Bukarica LG, Peric M, et al.Analysis of vasoreactivity of isolated human radial artery.J Pharmacol Sci, 2006, 100:34-40.
|
12. |
Gericke A, Steege A, Manicam C, et al.Role of the M3 muscarinic acetylcholine receptor subtype in murine ophthalmic arteries after endothelial removal. Invest Ophthalmol Vis Sci, 2014, 55:625-631.
|
- 1. 尹文, 李俊杰.感染性休克发病机制的研究进展.中国急救医学, 2015, 35:196-201.
- 2. Sheridan B C, Mcintyre R Jr, Moore E E, et al.Neutrophils mediate pulmonary vasomotor dysfunction in endotoxin-induced acute lung injury.J Trauma, 1997, 42:391-396.
- 3. Attinà TM, Oliver JJ, Malatino LS, et al. Contribution of the M3 muscarinic receptors to the vasodilator response to acetylcholine in the human forearm vascular bed.Br J Clin Pharmacol, 2008, 66:300-303.
- 4. 黄新莉, 周晓红, 韦鹏, 等.内源性硫化氢在脂多糖引起的肺动脉高压中的作用.生理学报, 2008, 60:211-215.
- 5. 齐小非, 张锦.感染性休克时肺动脉改变及调节机制的研究进展.中国危重病急救医学, 2008, 20:630-633.
- 6. 索良源, 张锦.去甲肾上腺素治疗感染性休克时对肺动、静脉血管压力的影响.中国呼吸与危重监护杂志, 2014, 13:508-512.
- 7. 佟冬怡, 张锦, 于泓波, 等.去甲肾上腺素和多巴胺对内毒素孵育兔肺动脉和体动脉环张力影响的比较.中国呼吸与危重监护杂志, 2010, 9:188-192.
- 8. 章静, 史佳, 余剑波, 等.P13K/Akt/Nrf2信号通路在兔内毒素休克诱发急性肺损伤中的作用.中华麻醉学杂志, 2015, 35:1257-1260.
- 9. Frostermann U, Pollock JS, Nakane M, et al. Noitric oxide synthases in the cardiovascular system. Trends Cardiovasc Med, 1993, 3:104-110.
- 10. 佟冬怡, 于泓波, 李娜, 等.预注不同剂量长托宁对内毒素休克兔肺动脉张力的影响及机制探讨.中国医科大学学报, 2011, 40:228-240.
- 11. Stojnic N, Bukarica LG, Peric M, et al.Analysis of vasoreactivity of isolated human radial artery.J Pharmacol Sci, 2006, 100:34-40.
- 12. Gericke A, Steege A, Manicam C, et al.Role of the M3 muscarinic acetylcholine receptor subtype in murine ophthalmic arteries after endothelial removal. Invest Ophthalmol Vis Sci, 2014, 55:625-631.