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PLoS One. 2019 Apr 24;14(4):e0215994. doi: 10.1371/journal.pone.0215994. eCollection 2019.

Inherited risk plus prenatal insult caused malignant dysfunction in mesenteric arteries in adolescent SHR offspring.

Author information

1
Institute for Fetology, First Hospital of Soochow University, Suzhou, Jiangsu, China.
2
Obstetrics and Gynecology, Municipal Hospital, Suzhou, Jiangsu, China.
3
Obstetrics and Gynecology, Tengzhou Central People's Hospital, Zaozhuang, Shandong, China.
4
Center for Prenatal Biology, Loma Linda University, Loma Linda, CA, United States of America.

Abstract

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.

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