孕期尼古丁暴露致成年子代大鼠中枢对血管紧张素II的高反应性

俞峰 张建国 高喜仁 董伟家 张志智 张博 夏志恒 张于娟*

doi:10.3969/j.issn.0529-1356.2013.02.003

解剖学报 ›› 2013, Vol. 44 ›› Issue (2) : 157-162. DOI: 10.3969/j.issn.0529-1356.2013.02.003

神经生物学

孕期尼古丁暴露致成年子代大鼠中枢对血管紧张素II的高反应性

俞峰¹ 张建国¹高喜仁¹ 董伟家¹张志智¹ 张博¹夏志恒¹ 张于^2* ..

作者信息 +

Prenatal nicotine exposure induces adult offspring high response to central angiotensin II

YU Feng¹ ZHANG Jian-guo¹GAO Xi-ren¹ DONG Wei-jia¹ ZHANG Zhi-zhi¹ ZHANG Bo¹ XIA Zhi-heng¹ZHANG Yu-juan ^2*

Author information +

文章历史 +

摘要

目的探讨孕期尼古丁暴露后，子代大鼠中枢对血管紧张素II（AngII）的反应性。方法对孕期尼古丁暴露的子代大鼠（n =7）脑室内注射AngII、洛沙坦(Los)和PD123319（PD）后，观察尼古丁子代（尼古丁组）平均动脉压（MAP）、血气与正常大鼠子代（对照组，n =7）之间的差异，并检测下丘脑前区（AHA）c-Fos表达，AngII受体1a（AT1aR）、AT1bR和AT2R mRNA的变化，以及AHA区AT1R、AT2R蛋白表达水平。结果尼古丁组基础MAP与对照组无差异，但脑室内注射 AngII后，尼古丁组大鼠MAP高于对照组［（120.36±6.23） mmHg （109.87±6.86）mmHg，P <0.05］，AHA区的c-Fos表达也明显强于对照组（25.8±2.91 比6.42±1.52，P <0.05），而Los预处理后，两组MAP无明显变化，但PD预处理后，尼古丁组MAP仍高于对照组。并且尼古丁组AHA区的AT1aR mRNA高于对照组（1.23±0.05 比 1.00， P <0.05），AT1R蛋白表达也高于对照组（0.581±0.06 比 0.353±0.05，P <0.05）。结论孕期尼古丁暴露可导致子代大鼠AHA区AT1aR mRNA及AT1R蛋白高于对照组，可能导致中枢对AngII的反应性增强。

Abstract

Objective To investigate the effect of prenatal nicotine exposure to the adult offspring response to central angiotensin. Methods The mean arterial pressure(MAP) and blood gas analysis after intracerebroventricular (ICV)injection of angiotensin II(AngII), losartan(Los), PD123319（PD）to nicotine offspring （nicotine, n =7）and control offspring（control, n =7） were tested. The angiotensin Ⅱ receptor 1 (AT1aR), AT1bR and AT2R mRNA, c-Fos protein, and AT1R, AT2R protein expression of anterior hypothalamic area(AHA) were detected. Results There was no difference between the control and nicotine groups, but after ICV AngII, the MAP was significantly higher in nicotine group than in the control group ［（120.36±6.23）mmHg vs （109.87±6.86）mmHg，P <0.05］. ICV Los in advance blocked the effect whereas ICV PD did not. The c-Fos expression was stronger in the nicotine group than that in the control group（25.8±2.91 vs 6.42±1.52, P< 0.05）. The AT1aR mRNA（1.23±0.05 vs 1.00，P < 0.05）and AT1R protein（0.581±0.06 vs 0.353±0.05，P <0.05）expression were higher in the nicotine group than that in the control group. Conclusion Prenatal nicotine exposure induces higher expression of AT1aR mRNA and AT1R protein, which may result in high response to central angiotensin II of adult offspring.

导出引用

俞峰张建国高喜仁董伟家张志智张博夏志恒张于娟*. 孕期尼古丁暴露致成年子代大鼠中枢对血管紧张素II的高反应性[J]. 解剖学报. 2013, 44(2): 157-162 https://doi.org/10.3969/j.issn.0529-1356.2013.02.003

YU Feng ZHANG Jian-guo GAO Xi-ren DONG Wei-jia ZHANG Zhi-zhi ZHANG Bo XIA Zhi-heng ZHANG Yu-juan * . Prenatal nicotine exposure induces adult offspring high response to central angiotensin II[J]. Acta Anatomica Sinica. 2013, 44(2): 157-162 https://doi.org/10.3969/j.issn.0529-1356.2013.02.003

参考文献

［1］ Lim R, Sobey CG. Maternal nicotine exposure and fetal programming of vascular oxidative stress in adult offspring［J］. Br J Pharmacol, 2011,164(5):1397-1399.

［2］ Slotkin TA. Fetal nicotine or cocaine exposure: which one is worse［J］? J harmacol Exp Ther, 1998,285（3）: 931-945.

［3］ Dichson SL, Hrabovszky E, and Hansson C, et al. Blockade of central nicotine acetylcholine receptor signaling attenuate ghrelin-induced food intake in rodents ［J］. Neuroscience， 2010,171(4):1180-1186.

［4］ Bruin JE, Gerstein HC， Holloway AC. Longterm consequences of fetal and neonatal nicotine exposure: a critical review［J］. Toxicol Sci

2010,116(2):364-374.

［5］ Winzer-Serhan UH. Long-term consequences of maternal smoking and developmental chronic nicotine exposure［J］. Front Biosci， 2008, 13:636-649.

［6］ Vargas F, Rodríguez-Gómez I, Vargas-Tendero P, et al. The renin-angiotensin system in thyroid disorders and its role in cardiovascular and renal

manifestations［J］. J Endocrinol， 2012,213(1):25-36. 

［7］ Xiao D, Xu Z, Huang X,et al. Prenatal gender-related nicotine exposure increases blood pressure response to angiotensin Ⅱ in adult offspring［J］. Hypertension, 2008, 51（4）:1239-1247.

［8］ Kubo T, Hagiwara Y. Enhanced central hypertonic saline-induced activation of angiotensin II-sensitive neurons in the anterior hypothalamic area of spontaneously hypertensive and Dahl S rats［J］. Brain Res

Bull,2006,68(5):335-340.

[9] Kubo T, Katsumata Y, Fukumori R, et al. Central nicotinic receptor blockade inhibits emotionally conditioned pressor responses in rats［J］. Experientia, 1996, 52 (4): 348-352.

[10]Ding Y, Lv J, Mao C,et al. High-salt diet during pregnancy and

angiotensin-related cardiac changes［J］. J Hypertens, 2010 ,28(6):1290-1297.

［1］ Guan J, Mao C, Xu F, et al.Low doses of nicotine induced fetal cardiovascular responses, hypoxia, and brain cellular activation in ovine fetuses［J］. Neurotoxicology, 2009,30(2):290-297.

［2］ Kubo T, Hagiwara Y. Enhanced central hypertonic saline-induced activation of angiotensin II-sensitive neurons in the anterior hypothalamic area of spontaneously hypertensive and Dahl S rats ［J］. Brain Res Bull, 2006,68(5):335-340. 

［3］ Feichao X, Caiping M, Lijun S, et al. Development of fetal brain renin-angiotensin system and hypertension programmed in fetal origins［J］. Prog Neurobiol, 2009 ,87(4):252-23. 

［4］ Guan J, Mao C,Feng X,et al. Fetal development of regulatory mechanisms for body fluid homeostasis［J］. Braz J Med Biol Res, 2008,41(6):446-454.

［5］ Nakadate K, Imamura K , Watanabe Y. Effects of monocular deprivation on the spatial pattern of visually induced expression of c-Fos protein［J］. Neuroscience,2012,27(202):17-28. 

［6］ Horiuchi M, Iwanami J, Mogi M. Regulation of angiotensin II receptors beyond the classical pathway ［J］. Clin Sci, 2012, 123 (4): 193-203.