Institute for Fetology, First Hospital of Soochow University, Suzhou, Jiangsu, China.
Obstetrics and Gynecology, Municipal Hospital, Suzhou, Jiangsu, China.
PLoS One. 2019 Apr 24;14(4):e0215994. doi: 10.1371/journal.pone.0215994. eCollection 2019.
Prenatal hypoxia can induce cardiovascular diseases in the offspring. This study determined whether and how prenatal hypoxia may cause malignant hypertension and impaired vascular functions in spontaneous hypertension rat (SHR) offspring at adolescent stage. Pregnant SHR were placed in a hypoxic chamber (11% O2) or normal environment (21% O2) from gestational day 6 until birth. Body weight and blood pressure (BP) of SHR offspring were measured every week from 5 weeks old. Mesenteric arteries were tested. Gestational hypoxia resulted in growth restriction during 6-12 weeks and a significant elevation in systolic pressure in adolescent offspring at 12 weeks old. Notably, endothelial vasodilatation of mesenteric arteries was impaired in SHR adolescent offspring exposed to prenatal hypoxia, vascular responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were reduced, as well as plasma nitric oxide levels and expression of endothelial nitric oxide synthase (eNOS) in vessels were decreased. Moreover, mesenteric arteries in SHR offspring following prenatal hypoxia showed enhanced constriction responses to phenylephrine (PE), associated with up-regulated activities of L-type calcium channel (Ca2+-dependent), RhoA/Rock pathway signaling (Ca2+-sensitization), and intracellular Ca2+ flow. Pressurized myograph demonstrated altered mechanical properties with aggravated stiffness in vessels, while histological analysis revealed vascular structural disorganization in prenatal hypoxia offspring. The results demonstrated that blood pressure and vascular function in young SHR offspring were affected by prenatal hypoxia, providing new information on development of hypertension in adolescent offspring with inherited hypertensive backgrounds.
产前缺氧可诱发后代心血管疾病。本研究旨在探讨产前缺氧是否以及如何导致青春期自发性高血压大鼠（SHR）后代发生恶性高血压和血管功能障碍。将妊娠 SHR 置于低氧室（11% O2）或正常环境（21% O2）中，从妊娠第 6 天持续至分娩。从 5 周龄开始，每周测量 SHR 后代的体重和血压（BP）。检测肠系膜动脉功能。妊娠期缺氧导致 6-12 周胎儿生长受限，12 周时青春期后代收缩压显著升高。值得注意的是，产前缺氧使 SHR 青春期后代肠系膜动脉内皮依赖性血管舒张功能受损，对乙酰胆碱（ACh）和硝普钠（SNP）的血管反应性降低，血浆一氧化氮水平和血管内皮型一氧化氮合酶（eNOS）表达降低。此外，产前缺氧的 SHR 后代肠系膜动脉对苯肾上腺素（PE）的收缩反应增强，与 L 型钙通道（依赖 Ca2+）、RhoA/Rock 通路信号（Ca2+敏化）和细胞内 Ca2+流的活性上调有关。加压肌动描记术显示血管力学特性发生改变，血管僵硬程度加重，组织学分析显示产前缺氧后代血管结构紊乱。结果表明，产前缺氧影响年轻 SHR 后代的血压和血管功能，为遗传性高血压背景下青春期后代高血压的发生提供了新的信息。
