Hydrogen Sulfide Attenuated Angiotensin II-Induced Sympathetic Excitation in Offspring of Renovascular Hypertensive Rats.

Hydrogen Sulfide Attenuated Angiotensin II-Induced Sympathetic Excitation in Offspring of Renovascular Hypertensive Rats.
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硫化氢减弱血管紧张素 II 诱导的肾血管性高血压大鼠后代的交感神经兴奋

DOI:
10.3389/fphar.2020.565726
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发表时间:
2020
影响因子:
5.6
通讯作者:
Wu Y
Wu Y
中科院分区:
医学2区
文献类型:
--
作者:
Feng X;Guo Q;Xue H;Duan X;Jin S;Wu Y

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目的大量研究表明,妊娠期父母的健康状况与成年子女的心血管疾病密切相关。本研究探讨了肾血管性高血压动物后代对血管紧张素II(Ang II)的敏感性是否增强,以及硫化氢(H2S)是否可以减弱后代对Ang II的反应。方法采用无创性尾袖容积描记法测定8 ~ 16周龄仔鼠的收缩压(SBP),每2周测量一次。侧脑室微量注射Ang Ⅱ后,记录血压、心率(HR)和肾交感神经活动(RSNA),以检测子代对Ang Ⅱ的反应。Western blot检测孤束核(NTS)中AT 1 R、AT 1 R-associated protein(ATRAP)、Nox 2、p67 phox和nitrotyrosine的蛋白表达。结果高血压大鼠子代的收缩压明显高于对照组,出生前或出生后给予硫化氢可明显改善上述效应。侧脑室微量注射Ang Ⅱ可引起高血压大鼠子代交感神经反应增强。高血压大鼠子代孤束核AT 1 R和氧化应激相关蛋白表达增加,ATRAP表达减少。出生前或出生后给予外源性H2S可改善上述效应。结论出生前或出生后给予H2S可抑制Ang Ⅱ诱导的高血压大鼠子代交感神经兴奋,其机制可能与调节NTS中AT 1 R和ATRAP的平衡,下调氧化应激相关蛋白表达有关。
Objective Numerous findings have demonstrated a strong association between parental health during pregnancy and cardiovascular disease in adult offspring. This study investigated whether sensitivity to angiotensin II (Ang II) is enhanced in offspring of renovascular hypertensive animals and whether hydrogen sulfide (H2S) can attenuate the increased response to Ang II in offspring. Method The systolic blood pressure (SBP) was measured by non-invasive tail-cuff plethysmograpy every two weeks in all offspring from 8 to 16 weeks. After intracerebroventricular microinjection of Ang II in the offspring, blood pressure, heart rate (HR), and renal sympathetic nerve activity (RSNA) were recorded to test the response to Ang II in the offspring. Western blot analysis was used to examine the protein expression of AT1R, AT1R-associated protein (ATRAP), Nox2, p67phox, and nitrotyrosine in the nucleus tractus solitarii (NTS). Results The SBP in the offspring of hypertensive rats were significantly higher than that in control group, and the above effects were significantly improved by prenatal or postnatal administration of H2S. Intralateroventricular microinjection of Ang II induced greater sympathetic responses in offspring of hypertensive rats than control group. The expression of AT1R and oxidative stress-related protein was increased, whereas that of ATRAP was decreased in the NTS in offspring of hypertensive rats. Exogenous administration of H2S prenatally or postnatally improved the above effects. Conclusion Prenatal or postnatal administration of H2S attenuated AngII-induced sympathetic excitation in offspring of hypertensive rats, which may occur by modulating the balance between AT1R and ATRAP and downregulating oxidative stress-related protein expression in the NTS.
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