Late gestational hypoxia and a postnatal high salt diet programs endothelial dysfunction and arterial stiffness in adult mouse offspring
Autor: | Tamara M. Paravicini, Tiffany Tan, Sarah L. Walton, Reetu R. Singh, Karen M. Moritz |
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Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Pregnancy Physiology Offspring Vasodilation 030204 cardiovascular system & hematology Biology Hypoxia (medical) medicine.disease 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Endocrinology Internal medicine medicine Arterial stiffness Weaning Sodium nitroprusside Endothelial dysfunction medicine.symptom medicine.drug |
Zdroj: | The Journal of Physiology. 594:1451-1463 |
ISSN: | 0022-3751 |
DOI: | 10.1113/jp271067 |
Popis: | Gestational hypoxia and high dietary salt intake have both been associated with impaired vascular function in adulthood. Using a mouse model of prenatal hypoxia, we examined whether a chronic high salt diet had an additive effect in promoting vascular dysfunction in offspring. Pregnant CD1 dams were placed in a hypoxic chamber (12% O2) or housed under normal conditions (21% O2) from embryonic day 14.5 until birth. Gestational hypoxia resulted in a reduced body weight for both male and female offspring at birth. This restriction in body weight persisted until weaning, after which the animals underwent catch-up growth. At 10 weeks of age, a subset of offspring was placed on a high salt diet (5% NaCl). Pressurized myography of mesenteric resistance arteries at 12 months of age showed that both male and female offspring exposed to maternal hypoxia had significantly impaired endothelial function, as demonstrated by impaired vasodilatation to ACh but not sodium nitroprusside. Endothelial dysfunction caused by prenatal hypoxia was not exacerbated by postnatal consumption of a high salt diet. Prenatal hypoxia increased microvascular stiffness in male offspring. The combination of prenatal hypoxia and a postnatal high salt diet caused a leftward shift in the stress-strain relationship in both sexes. Histopathological analysis of aortic sections revealed a loss of elastin integrity and increased collagen, consistent with increased vascular stiffness. These results demonstrate that prenatal hypoxia programs endothelial dysfunction in both sexes. A chronic high salt diet in postnatal life had an additive deleterious effect on vascular mechanics and structural characteristics in both sexes. |
Databáze: | OpenAIRE |
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