Intermittent maternal hypoxia has an influence on regional expression of endothelial nitric oxide synthase in fetal arteries of rabbits

Abstract

Background: Maternal hypoxia induces sustained fetal adaptations associated with changes in gene expression. We hypothesized that intermittent maternal hypoxia has an influence on regional expression of endothelial nitric oxide synthase (eNOS) in fetal arteries of New Zealand White rabbits. Methods: Timed-pregnant New Zealand White rabbits (term = 30 ± 1 d) were randomly assigned to a normoxic control group (n = 5) or a hypoxia group (12% O 2 , n = 5) during days 10-29 of pregnancy. At the end of pregnancy (29 d gestation), blood samples were collected from mothers and fetuses. Carotid and femoral arteries of fetuses were extracted for eNOS mRNA and protein concentration and analysis of total NOS activities. results: Our data demonstrate that chronic intermittent maternal hypoxia significantly increased eNOS mRNA and protein concentrations and total NOS activities in carotid artery segments but decreased eNOS mRNA and protein concentrations and total NOS activities in femoral artery segments in the same fetuses. Vascular endothelial cells, but not smooth muscle cells, of fetal rabbits exhibited positive immunostaining for the eNOS protein. conclusion: These observations suggest that chronic hypoxia can regulate regional expression of eNOS as an adaptive response to hypoxic stress in fetal arteries.

Non-muscular myosin light chain kinase triggers intermittent hypoxia-induced interleukin-6 release, endothelial dysfunction and permeability

“…Indeed, in skin biopsies, it has been reported an increase in eNOS mRNA expression in severely hypoxemic OSA patients 16 . At the vascular level, an increase of eNOS expression and activity has been described in carotid arteries from fetal rabbits exposed to IH 22 . Also, in hypertensive rats, IH induced formation of available NO stores and enhanced the capacity of aortic rings to store NO improving endothelial function 23 .…”

Prenatal Hypoxia Affects Foetal Cardiovascular Regulatory Mechanisms in a Sex- and Circadian-Dependent Manner: A Review

“…The consequences of hypoxia on the expression of eNOS are contradictory. Some studies show increased eNOS in the carotid artery and decreased in the femoral artery [ 57 ] at the protein and gene expression levels [ 59 ]. In the heart, eNOS expression was increased at the protein and decreased at the gene expression level [ 85 ].…”

“…Under normoxia, HIF-1α is rapidly degraded, but if the partial pressure of oxygen decreases, it is stabilized and accumulates in the cells. HIF-1α maintains oxygen homeostasis by regulating the expression of hundreds of genes and interacts with pathways involved in the regulation of the cardiovascular system, such as the chemoreflex, sympathetic drive [ 54 ], renin-angiotensin-aldosterone system (RAAS) [ 55 , 56 ], and local vessel wall components such as nitric oxide (NO) [ 57 , 58 , 59 ] and endothelin-1 [ 60 , 61 ]. Moreover, HIF directly interacts with the circadian clock because HIF-1α controls the expression of several canonical circadian genes and the response to hypoxia is gated by the circadian clock [ 62 ].…”

In Utero Origins of Hypertension: Mechanisms and Targets for Therapy

“…In a few studies, however, the opposite has been observed. For instance, in mesenteric and carotid arteries of protein restricted or hypoxic models, eNOS expression has been shown to be increased (71,328). Corresponding to the majority of evidence for reduced eNOS expression or activity, NO-mediated mesenteric artery vasodilation (265,266) , BH 4 is oxidized to the BH 3 · radical and then to BH 2 reducing its availability to eNOS.…”