Guo Qi, Feng Xiaohong, Xue Hongmei, Jin Sheng, Teng Xu, Duan Xiaocui, Xiao Lin, Wu Yuming
Department of Physiology, Hebei Medical University, Shijiazhuang, China.
Department of Laboratory Diagnostics, Hebei Medical University, Shijiazhuang, China.
Front Physiol. 2019 Sep 19;10:1184. doi: 10.3389/fphys.2019.01184. eCollection 2019.
Increasing evidence indicates there is a strong association between parental health during pregnancy and incidence of cardiovascular disease in adult offspring. Recently, hydrogen sulfide (HS) has been demonstrated to be a powerful vasodilator of the placental vasculature, improving intrauterine growth restriction. In this study, we investigated whether parental hypertension induces autonomic dysfunction in male adult offspring, and the HS mechanism underlying this autonomic dysfunction. 2-kidney-1-clip method was employed to induce parental hypertension during pregnancy and lactation in rats. Basal blood pressure (BP) and autonomic function of male offspring in adulthood was evaluated. Additionally, either maternal hypertensive dams or their male offspring after weaning were treated with HS to determine improving effects of HS on autonomic dysfunction. The BP was significantly increased in male offspring of renovascular hypertensive dams when compared to that in offspring of normotensive dams. The offspring of renovascular hypertensive dams also exhibited blunted baroreflex sensitivity, increased sympathetic effect and sympathetic tonus. Western blotting analysis revealed downregulation of endogenous HS catalyzed enzyme and upregulation of angiotensin Ang II type 1 receptor (AT1R) pathway in the nucleus tractus solitarius and rostral ventrolateral medulla, two hindbrain nuclei involved in BP and autonomic regulation, in these offspring. Either prenatal or postnatal treatment with HS improved the adverse effects. The results suggest that parental hypertension results in elevated BP and autonomic dysfunction in adult male offspring through activation of AT1R pathway and inhibition of endogenous HS production in the brain.
越来越多的证据表明，孕期父母的健康状况与成年后代心血管疾病的发病率之间存在密切关联。最近，硫化氢（HS）已被证明是胎盘血管的一种强大血管舒张剂，可改善子宫内生长受限。在本研究中，我们调查了父母高血压是否会导致成年雄性后代出现自主神经功能障碍，以及这种自主神经功能障碍背后的HS机制。采用双肾单夹法诱导大鼠孕期和哺乳期父母患高血压。评估成年雄性后代的基础血压（BP）和自主神经功能。此外，对患有高血压的母鼠或其断奶后的雄性后代进行HS治疗，以确定HS对自主神经功能障碍的改善作用。与血压正常的母鼠后代相比，肾血管性高血压母鼠的雄性后代血压显著升高。肾血管性高血压母鼠的后代还表现出压力反射敏感性降低、交感神经效应增加和交感神经张力增加。蛋白质印迹分析显示，在这些后代中，孤束核和延髓头端腹外侧髓质（参与血压和自主神经调节的两个后脑核）中，内源性HS催化酶下调，血管紧张素1型受体（AT1R）途径上调。产前或产后HS治疗均可改善这些不良影响。结果表明，父母高血压通过激活AT1R途径和抑制大脑中内源性HS的产生，导致成年雄性后代血压升高和自主神经功能障碍。
