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Hypertension Programmed in Adult Hens by Isolated Effects of Developmental Hypoxia In Ovo

In mammals, pregnancy complicated by chronic hypoxia can program hypertension in the adult offspring. However, mechanisms remain uncertain because the partial contributions of the challenge on the placenta, mother, and fetus are difficult to disentangle. Here, we used chronic hypoxia in the chicken...

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Autores principales: Skeffington, Katie L., Beck, Christian, Itani, Nozomi, Niu, Youguo, Shaw, Caroline J., Giussani, Dino A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott, Williams & Wilkins 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340221/
https://www.ncbi.nlm.nih.gov/pubmed/32536277
http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15045
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author Skeffington, Katie L.
Beck, Christian
Itani, Nozomi
Niu, Youguo
Shaw, Caroline J.
Giussani, Dino A.
author_facet Skeffington, Katie L.
Beck, Christian
Itani, Nozomi
Niu, Youguo
Shaw, Caroline J.
Giussani, Dino A.
author_sort Skeffington, Katie L.
collection PubMed
description In mammals, pregnancy complicated by chronic hypoxia can program hypertension in the adult offspring. However, mechanisms remain uncertain because the partial contributions of the challenge on the placenta, mother, and fetus are difficult to disentangle. Here, we used chronic hypoxia in the chicken embryo—an established model system that permits isolation of the direct effects of developmental hypoxia on the cardiovascular system of the offspring, independent of additional effects on the mother or the placenta. Fertilized chicken eggs were exposed to normoxia (N; 21% O(2)) or hypoxia (H; 13.5%–14% O(2)) from the start of incubation (day 0) until day 19 (hatching, ≈day 21). Following hatching, all birds were maintained under normoxic conditions until ≈6 months of adulthood. Hypoxic incubation increased hematocrit (+27%) in the chicken embryo and induced asymmetrical growth restriction (body weight, −8.6%; biparietal diameter/body weight ratio, +7.5%) in the hatchlings (all P<0.05). At adulthood (181±4 days), chickens from hypoxic incubations remained smaller (body weight, −7.5%) and showed reduced basal and stimulated in vivo NO bioavailability (pressor response to NG-nitro-L-arginine methyl ester, −43%; phenylephrine pressor response during NO blockade, −61%) with significant hypertension (mean arterial blood pressure, +18%), increased cardiac work (ejection fraction, +12%; fractional shortening, +25%; enhanced baroreflex gain, +456%), and left ventricular wall thickening (left ventricular wall volume, +36%; all P<0.05). Therefore, we show that chronic hypoxia can act directly on a developing embryo to program hypertension, cardiovascular dysfunction, and cardiac wall remodeling in adulthood in the absence of any maternal or placental effects.
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spelling pubmed-73402212020-08-05 Hypertension Programmed in Adult Hens by Isolated Effects of Developmental Hypoxia In Ovo Skeffington, Katie L. Beck, Christian Itani, Nozomi Niu, Youguo Shaw, Caroline J. Giussani, Dino A. Hypertension Original Articles In mammals, pregnancy complicated by chronic hypoxia can program hypertension in the adult offspring. However, mechanisms remain uncertain because the partial contributions of the challenge on the placenta, mother, and fetus are difficult to disentangle. Here, we used chronic hypoxia in the chicken embryo—an established model system that permits isolation of the direct effects of developmental hypoxia on the cardiovascular system of the offspring, independent of additional effects on the mother or the placenta. Fertilized chicken eggs were exposed to normoxia (N; 21% O(2)) or hypoxia (H; 13.5%–14% O(2)) from the start of incubation (day 0) until day 19 (hatching, ≈day 21). Following hatching, all birds were maintained under normoxic conditions until ≈6 months of adulthood. Hypoxic incubation increased hematocrit (+27%) in the chicken embryo and induced asymmetrical growth restriction (body weight, −8.6%; biparietal diameter/body weight ratio, +7.5%) in the hatchlings (all P<0.05). At adulthood (181±4 days), chickens from hypoxic incubations remained smaller (body weight, −7.5%) and showed reduced basal and stimulated in vivo NO bioavailability (pressor response to NG-nitro-L-arginine methyl ester, −43%; phenylephrine pressor response during NO blockade, −61%) with significant hypertension (mean arterial blood pressure, +18%), increased cardiac work (ejection fraction, +12%; fractional shortening, +25%; enhanced baroreflex gain, +456%), and left ventricular wall thickening (left ventricular wall volume, +36%; all P<0.05). Therefore, we show that chronic hypoxia can act directly on a developing embryo to program hypertension, cardiovascular dysfunction, and cardiac wall remodeling in adulthood in the absence of any maternal or placental effects. Lippincott, Williams & Wilkins 2020-06-15 2020-08 /pmc/articles/PMC7340221/ /pubmed/32536277 http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15045 Text en © 2020 The Authors. Hypertension is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.
spellingShingle Original Articles
Skeffington, Katie L.
Beck, Christian
Itani, Nozomi
Niu, Youguo
Shaw, Caroline J.
Giussani, Dino A.
Hypertension Programmed in Adult Hens by Isolated Effects of Developmental Hypoxia In Ovo
title Hypertension Programmed in Adult Hens by Isolated Effects of Developmental Hypoxia In Ovo
title_full Hypertension Programmed in Adult Hens by Isolated Effects of Developmental Hypoxia In Ovo
title_fullStr Hypertension Programmed in Adult Hens by Isolated Effects of Developmental Hypoxia In Ovo
title_full_unstemmed Hypertension Programmed in Adult Hens by Isolated Effects of Developmental Hypoxia In Ovo
title_short Hypertension Programmed in Adult Hens by Isolated Effects of Developmental Hypoxia In Ovo
title_sort hypertension programmed in adult hens by isolated effects of developmental hypoxia in ovo
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340221/
https://www.ncbi.nlm.nih.gov/pubmed/32536277
http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15045
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