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The Long-Term Effects of Prenatal Hypoxia on Coronary Artery Function of the Male and Female Offspring
Nataliia Hula1,2, Ricky Liu1,2, Floor Spaans2
1Department of Physiology, University of Alberta, Edmonton, AB T6G 2R3, Canada.
Insights
Prenatal hypoxia impairs adult offspring
Area of Science:
- Cardiovascular Physiology
- Developmental Biology
- Pharmacology
Background:
- Prenatal hypoxia is a known risk factor for adult cardiovascular dysfunction.
- Understanding the long-term vascular effects of prenatal hypoxia is crucial for developing preventative strategies.
Purpose of the Study:
- To investigate the long-term effects of prenatal hypoxia on coronary artery vasoconstrictive and vasodilative mechanisms in adult male and female offspring.
- To elucidate the specific pathways involved in impaired vascular function.
Main Methods:
- Wire myography was used to assess endothelium-dependent relaxation and vasoconstriction in rat coronary arteries.
- Pharmacological agents were used to inhibit nitric oxide synthase, prostaglandin H synthase, and endothelin B receptors.
- Gene expression of eNOS and PGHS-1/2 was analyzed.
Main Results:
- Prenatal hypoxia impaired endothelium-dependent vasodilation in both male and female offspring at 4 and 9.5 months.
- Impaired vasodilation was partly mediated by increased prostaglandin H synthase-dependent vasoconstriction.
- Endothelin-1 mediated responses were reduced in adult female offspring exposed to prenatal hypoxia.
- Coronary artery contractile capacity was impaired only in females.
Conclusions:
- Prenatal hypoxia induces long-term impairments in coronary artery vasodilation in adult offspring.
- Sex-specific differences exist in the contractile dysfunction following prenatal hypoxia.
- These findings highlight potential therapeutic targets for cardiovascular disease programmed by prenatal hypoxia.
Abstract:
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.
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