Zhang Zhongming, Zhang Yijing, Wang Yan, Ding Shengchen, Wang Chenhui, Gao Li, Johnson Alan, Xue Baojian
1 Zhang Zhongjing College of Chinese Medicine, Henan Key Laboratory of Zhang Zhongjing's Formulea for Immunoregulation, Nanyang Institute of Technology, China.
2 Department of Psychological and Brain Sciences, University of Iowa, USA.
J Renin Angiotensin Aldosterone Syst. 2019 Jan-Mar;20(1):1470320319834406. doi: 10.1177/1470320319834406.
: Brain-derived neurotropic factor (BDNF) is expressed throughout the central nervous system and peripheral organs involved in the regulation of blood pressure, but the systemic effects of BDNF in the control of blood pressure are not well elucidated.
: We utilized loxP flanked BDNF male mice to cross with nestin-Cre female mice to generate nerve system BDNF knockdown mice, nestin-BDNF (+/-), or injected Cre adenovirus into the subfornical organ to create subfornical organ BDNF knockdown mice. Histochemistry was used to verify injection location. Radiotelemetry was employed to determine baseline blood pressure and pressor response to angiotensin II (1000 ng/kg/min). Real-time polymerase chain reaction was used to measure the expression of renin-angiotensin system components in the laminal terminalis and peripheral organs.
: Nestin-BDNF (+/-) mice had lower renin-angiotensin system expression in the laminal terminalis and peripheral organs including the gonadal fat pad, and a lower basal blood pressure. They exhibited an attenuated hypertensive response and a weak or similar modification of renin-angiotensin system component expression to angiotensin II infusion. Subfornical organ BDNF knockdown was sufficient for the attenuation of angiotensin II-induced hypertension.
: Central BDNF, especially subfornical organ BDNF is involved in the maintenance of basal blood pressure and in augmentation of hypertensive response to angiotensin II through systemic regulation of the expression of renin-angiotensin system molecules.
脑源性神经营养因子（BDNF）在整个中枢神经系统以及参与血压调节的外周器官中均有表达，但BDNF在血压控制中的全身效应尚未得到充分阐明。
我们利用loxP侧翼的BDNF雄性小鼠与巢蛋白-Cre雌性小鼠杂交，以产生神经系统BDNF敲低小鼠，即巢蛋白-BDNF（+/-），或者将Cre腺病毒注射到穹窿下器官，以创建穹窿下器官BDNF敲低小鼠。采用组织化学方法验证注射部位。利用无线电遥测技术测定基线血压以及对血管紧张素II（1000 ng/kg/min）的升压反应。运用实时聚合酶链反应测量终板和外周器官中肾素-血管紧张素系统成分的表达。
巢蛋白-BDNF（+/-）小鼠在终板以及包括性腺脂肪垫在内的外周器官中的肾素-血管紧张素系统表达较低，且基础血压较低。它们对血管紧张素II输注的高血压反应减弱，肾素-血管紧张素系统成分表达的改变较弱或相似。穹窿下器官BDNF敲低足以减弱血管紧张素II诱导的高血压。
中枢BDNF，尤其是穹窿下器官BDNF，通过对肾素-血管紧张素系统分子表达的全身调节，参与基础血压的维持以及对血管紧张素II高血压反应的增强。
