Gestational chronic intermittent hypoxia induces hypertension, proteinuria, and fetal growth restriction in mice

Weng, Cui-Lian; Huang, Long; Feng, Hangwei; He, Quan-ying; Lin, Xingsheng; Jiang, Tingting; Lin, Jian; Wang, Xincai; Liu, Qinghua

doi:10.1007/s11325-021-02529-3

Cited by 7 publications

(6 citation statements)

References 27 publications

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“…This suggests that IH exposures did not influence fetal growth or placental development by GD 21. These findings contrast with those reported in a mice model, where the authors documented decreased litter size, fetal weight, and placental weight of IH-exposed mice on GD 20 [7]. Discrepancies in experimental protocols, such as the duration of IH exposure, may account for the disparate results obtained.…”

Section: Discussioncontrasting

confidence: 86%

“…Accumulating evidence strongly supports the notion that insults experienced during intrauterine development, particularly IH, often result in adverse outcomes in offspring [7,27,34]. However, in the present study, we observed no significant differences in litter size, fetal weight, or placental weight between IH and control rats.…”

Section: Discussionsupporting

confidence: 81%

“…Discrepancies in experimental protocols, such as the duration of IH exposure, may account for the disparate results obtained. Specifically, in the mice study [7], IH exposure commenced from GD 1 until GD 20, while in our study, IH exposure was limited to the late gestational period (GD 10–21), which aligns more closely with clinical relevance given that most pregnant women develop OSA during the third trimester. Interestingly, in our previous study employing the same animal model [27], we did observe reduced offspring weights at birth in the IH group, indicating that fetal growth during the final day of gestation might have been affected.…”

Section: Discussionmentioning

confidence: 62%

“…However, the causal relationship between OSA and gestational hypertension has not been sufficiently validated. One study, utilizing a mouse model, has demonstrated a link between chronic IH exposure and gestational hypertension [7] without delving into the underlying mechanisms. Our study reveals that exposure to IH during the latter stages of gestation leads to elevated BP.…”

Section: Discussionmentioning

confidence: 99%

“…Although the exact etiology of HDP remains elusive, a growing body of evidence has revealed an association between HDP and OSA and highlighted the potential significance of OSA-related hypoxia in the pathophysiology and origins of HDP. Specifically, studies in pregnant mice demonstrated that exposure to gestational IH, the hallmark feature of OSA, increased systolic blood pressure (BP) and induced preeclampsia-like symptoms [7]. Another mouse study showed that gestational IH impaired uterine artery function with reduced endothelium-dependent vasodilation [8].…”

Section: Introductionmentioning

confidence: 99%

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Gestational intermittent hypoxia induces endothelial dysfunction and hypertension in pregnant rats: role of endothelin type B receptor

Song,

Yadav,

Dangudubiyyam

et al. 2023

Biology of Reproduction

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Obstructive sleep apnea (OSA) is a recognized risk factor for gestational hypertension, yet the exact mechanism behind this association remains unclear. Here, we tested the hypothesis that intermittent hypoxia (IH), a hallmark of OSA, induces gestational hypertension through perturbed endothelin-1 signaling. Pregnant Sprague–Dawley rats were subjected to normoxia (control), mild IH (mIH, 10.5% O2), or severe IH (sIH, 6.5% O2) from gestational day 10–21. Blood pressure (BP) was monitored. Plasma was collected and mesenteric arteries were isolated for myograph and protein analyses. The mIH and sIH groups demonstrated elevated BP, reduced plasma nitrate/nitrite (NOx), and unchanged endothelin-1 levels compared to the control group. Western blot analysis revealed decreased expression of endothelin type B receptor (ETBR) and phosphorylated endothelial nitric oxide synthase (eNOS), while the levels of endothelin type A receptor (ETAR) and total eNOS remained unchanged following IH exposure. The contractile responses to potassium chloride, phenylephrine, and endothelin-1 were unaffected in endothelium-denuded arteries from mIH and sIH rats. However, mIH and sIH rats exhibited impaired endothelium-dependent vasorelaxation responses to ETBR agonist IRL-1620 and acetylcholine compared to controls. Endothelium denudation abolished IRL-1620-induced vasorelaxation, supporting the involvement of endothelium in ETBR-mediated relaxation. Treatment with IRL-1620 during IH exposure significantly attenuated IH-induced hypertension in pregnant rats. This was associated with elevated circulating NOx levels, enhanced ETBR expression, increased eNOS activation, and improved vasodilation responses. Our data suggested that IH exposure during gestation increases BP in pregnant rats by suppressing ETBR-mediated signaling, providing a molecular mechanism linking IH and gestational hypertension.

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Section: Discussioncontrasting

confidence: 86%

Section: Discussionsupporting

confidence: 81%