The Long-Term Effects of Prenatal Hypoxia on Coronary Artery Function of the Male and Female Offspring

Nataliia Hula; Ricky Liu; Floor Spaans; Mazhar Pasha; Anita Quon; Raven Kirschenman; Christy-Lynn M. Cooke; Sandra T. Davidge

doi:10.3390/biomedicines10123019

Biomedicines (Nov 2022)

The Long-Term Effects of Prenatal Hypoxia on Coronary Artery Function of the Male and Female Offspring

Nataliia Hula,
Ricky Liu,
Floor Spaans,
Mazhar Pasha,
Anita Quon,
Raven Kirschenman,
Christy-Lynn M. Cooke,
Sandra T. Davidge

Affiliations

Nataliia Hula: Department of Physiology, University of Alberta, Edmonton, AB T6G 2R3, Canada
Ricky Liu: Department of Physiology, University of Alberta, Edmonton, AB T6G 2R3, Canada
Floor Spaans: Department of Obstetrics and Gynecology, Women and Children’s Health Research Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada
Mazhar Pasha: Department of Physiology, University of Alberta, Edmonton, AB T6G 2R3, Canada
Anita Quon: Department of Obstetrics and Gynecology, Women and Children’s Health Research Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada
Raven Kirschenman: Department of Obstetrics and Gynecology, Women and Children’s Health Research Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada
Christy-Lynn M. Cooke: Department of Obstetrics and Gynecology, Women and Children’s Health Research Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada
Sandra T. Davidge: Department of Physiology, University of Alberta, Edmonton, AB T6G 2R3, Canada

DOI: https://doi.org/10.3390/biomedicines10123019
Journal volume & issue: Vol. 10, no. 12
p. 3019

Abstract

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Prenatal hypoxia predisposes the offspring to the development of cardiovascular (CV) dysfunction in adult life. Using a rat model, we assessed the effect of prenatal hypoxia on vasoconstrictive and vasodilative mechanisms in left anterior descending coronary arteries of 4- and 9.5-month-old offspring. Endothelium-dependent relaxation to methylcholine and vasoconstriction responses to endothelin-1 (ET-1) were assessed by wire myography. Prenatal hypoxia impaired endothelium-dependent vasodilation in 4- and 9.5-month-old offspring. Inhibition of nitric oxide (NO) synthase prevented coronary artery relaxation in all groups. Inhibition of prostaglandin H synthase (PGHS) improved relaxation in prenatally hypoxic males and tended to improve vasorelaxation in females, suggesting that impaired vasodilation was mediated via increased PGHS-dependent vasoconstriction. An enhanced contribution of endothelium-dependent hyperpolarization to coronary artery vasodilation was observed in prenatally hypoxic males and females. No changes in endothelial NO synthase (eNOS) and PGHS-1 expressions were observed, while PGHS-2 expression was decreased in only prenatally hypoxic males. At 4 months, ET-1 responses were similar between groups, while ETB inhibition (with BQ788) tended to decrease ET-1-mediated responses in only prenatally hypoxic females. At 9.5 months, ET-1-mediated responses were decreased in only prenatally hypoxic females. Our data suggest that prenatal hypoxia has long-term similar effects on the mechanisms of impaired endothelium-dependent vasodilation in coronary arteries from adult male and female offspring; however, coronary artery contractile capacity is impaired only in prenatally hypoxic females. Understanding the mechanistic pathways involved in the programming of CV disease may allow for the development of therapeutic interventions.

Published in Biomedicines

ISSN: 2227-9059 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: http://www.mdpi.com/journal/biomedicines

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