Prenatal hypoxia enhanced angiotensin II-mediated vasoconstriction via increased oxidative signaling in fetal rats.

Toxic factors could cause in utero hypoxia, and prenatal hypoxia (PH) increased incidence of cardiovascular diseases in late life. It is unclear whether/how PH causes vascular injury during fetal life. This study found that PH significantly increased angiotensin II (Ang II)-mediated vessel contractions in fetal thoracic aortas, which was blocked by losartan, not PD123319, indicating that AT1 receptors played a dominant role in the enhanced fetal vasoconstriction following hypoxia. Prenatal hypoxia increased superoxide production and decreased superoxide dismutase (SOD) expression, associated with the enhanced NADPH oxidase (Nox) 4, but not Nox1 or Nox2 in fetal aortas. Ang II-increased vasoconstriction was inhibited by Nox inhibitor apocynin and SOD mimetic blocker tempol. These findings suggested that PH resulted in Ang II/AT1R-mediated fetal vascular hypertensive re-activity via pathways of Nox4-dependent oxidative stress, providing new information regarding the impact of PH on the functional and molecular development of fetal vascular systems.