Parental Renovascular Hypertension-Induced Autonomic Dysfunction in Male Offspring Is Improved by Prenatal or Postnatal Treatment With Hydrogen Sulfide
Parental Renovascular Hypertension-Induced Autonomic Dysfunction in Male Offspring Is Improved by Prenatal or Postnatal Treatment With Hydrogen Sulfide
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通过产前或产后硫化氢治疗可改善男性后代中父母肾血管性高血压引起的自主神经功能障碍
DOI：
10.3389/fphys.2019.01184
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发表时间：
2019-09-19
影响因子：
4
通讯作者：
Wu, Yuming
中科院分区：
文献类型：
--
作者：
Guo, Qi;Feng, Xiaohong;Wu, Yuming
越来越多的证据表明，怀孕期间父母的健康状况与成年后代的心血管疾病发病率之间存在密切联系。最近，硫化氢（H2S）已被证明是一个强大的胎盘血管扩张剂，改善宫内生长受限。在这项研究中，我们调查了父母的高血压是否会导致男性成年后代的自主神经功能障碍，以及这种自主神经功能障碍的H2S机制。采用2肾1夹法建立大鼠妊娠期和哺乳期高血压模型。测定雄性子代成年期基础血压和自主神经功能。此外，无论是母亲的高血压母鼠或断奶后的雄性后代与硫化氢处理，以确定改善效果的硫化氢对自主神经功能障碍。肾血管性高血压母鼠的雄性后代的血压显著高于血压正常母鼠的后代。肾血管性高血压母鼠的后代也表现出压力反射敏感性减弱，交感效应和交感紧张性增加。Western blotting分析显示，下调内源性H2S催化酶和上调血管紧张素Ⅱ受体1型（AT1R）通路在孤束核和延髓头端腹外侧，两个后脑核参与BP和自主神经调节，在这些后代。无论是产前或产后治疗与H2S改善的不良反应。结果提示，双亲高血压通过激活AT1R通路，抑制脑内内源性H2S的产生，导致成年雄性后代血压升高和自主神经功能紊乱。
Increasing evidence indicates there is a strong association between parental health during pregnancy and incidence of cardiovascular disease in adult offspring. Recently, hydrogen sulfide (H2S) 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 H2S 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 H2S to determine improving effects of H2S 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 H2S 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 H2S 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 H2S production in the brain.