Feng Xiaohong, Guo Qi, Xue Hongmei, Duan Xiaocui, Jin Sheng, Wu Yuming
Department of Laboratory Diagnostics, Hebei Medical University, Shijiazhuang, China.
Experimental Center for Teaching, Hebei Medical University, Shijiazhuang, China.
Front Pharmacol. 2020 Sep 11;11:565726. doi: 10.3389/fphar.2020.565726. eCollection 2020.
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 (HS) 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, p67, 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 HS. 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 HS prenatally or postnatally improved the above effects. CONCLUSION: Prenatal or postnatal administration of HS 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.
目的:众多研究结果表明孕期父母的健康状况与成年子代的心血管疾病之间存在密切关联。本研究调查了肾血管性高血压动物的子代对血管紧张素 II(Ang II)的敏感性是否增强,以及硫化氢(HS)是否能减弱子代对 Ang II 增强的反应。 方法:在所有子代 8 至 16 周龄期间,每两周通过无创尾袖体积描记法测量收缩压(SBP)。在子代脑室内微量注射 Ang II 后,记录血压、心率(HR)和肾交感神经活动(RSNA),以测试子代对 Ang II 的反应。采用蛋白质免疫印迹分析检测孤束核(NTS)中 AT1R、AT1R 相关蛋白(ATRAP)、Nox2、p67 和硝基酪氨酸的蛋白表达。 结果:高血压大鼠子代的 SBP 显著高于对照组,产前或产后给予 HS 可显著改善上述影响。脑室内注射 Ang II 后,高血压大鼠子代比对照组诱发更强的交感反应。高血压大鼠子代 NTS 中 AT1R 和氧化应激相关蛋白的表达增加,而 ATRAP 的表达降低。产前或产后给予外源性 HS 可改善上述影响。 结论:产前或产后给予 HS 可减弱 Ang II 诱导的高血压大鼠子代的交感兴奋,这可能是通过调节 AT1R 和 ATRAP 之间的平衡以及下调 NTS 中氧化应激相关蛋白的表达来实现的。
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