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Enhanced oxidative stress as a potential mechanism underlying the programming of hypertension in utero
Maria do Carmo P Franco1, Ana Paula V Dantas, Eliana Hiromi Akamine
1Laboratory of Hypertension, Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, SP, Brazil. mdcfranco@yahoo.com
Insights
Maternal undernutrition in pregnant rats leads to hypertension and impaired blood vessel function in offspring. This is linked to increased oxidative stress and reduced antioxidant activity, impacting fetal development.
Area of Science:
- Developmental biology
- Cardiovascular physiology
- Nutritional science
Background:
- Maternal undernutrition impairs fetal growth and increases risks for adult diseases like hypertension.
- Endothelial dysfunction is a characteristic of these diseases and may be linked to oxidative stress.
Purpose of the Study:
- To investigate the impact of intrauterine undernutrition on oxidative stress.
- To determine the consequences of oxidative stress on mesenteric arteriolar responses to vasoactive agents in offspring.
Main Methods:
- Pregnant Wistar rats were fed normal or restricted diets (50% intake).
- Offspring blood pressure, mesenteric arteriolar reactivity, and superoxide anion generation were assessed.
- Superoxide dismutase activity was measured in the mesentery.
Main Results:
- Intrauterine undernutrition resulted in hypertension and reduced vasodilation to acetylcholine and bradykinin.
- Superoxide dismutase activity was decreased, and superoxide anion concentration was increased in offspring from diet-restricted dams.
- Administration of superoxide dismutase or its mimetic improved arteriolar responses.
Conclusions:
- Intrauterine undernutrition enhances in vivo oxidative stress in offspring.
- This oxidative stress is directly related to impaired endothelium-dependent vasodilation.
- Findings link maternal dietary restriction during gestation to long-term cardiovascular dysfunction via oxidative stress pathways.
Abstract:
Maternal undernutrition during critical periods of organ development is known to impair fetal growth and predispose to the development of adulthood diseases, such as hypertension, coronary heart disease and type II diabetes that are linked to low birth weight and are characterized by endothelial dysfunction. Increased oxidative stress, in rats submitted to intrauterine undernutrition, provides a potential explanation for the endothelial dysfunction development. The aim of this study was to determine the oxidative stress and its consequence on mesenteric arteriolar responses to vasoactive agents in offspring from diet-restricted dams. For this, female pregnant Wistar rats were fed either normal or 50% of normal intake diets, during the whole gestational period. In male offspring, arterial blood pressure was determined by the tail cuff method in anesthetized rats, mesenteric arteriolar reactivity and superoxide anion generation were studied using intravital microscopy and superoxide dismutase activity was determined in mesentery by spectrophotometric assay. Intrauterine undernutrition induced hypertension, decreased vasodilation to acetylcholine and bradykinin but did not alter the responses to sodium nitroprusside. Topical application of superoxide dismutase and superoxide dismutase mimetic manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin significantly improved the altered arteriolar responses to acetylcholine and bradykinin. A decreased superoxide dismutase activity and an increased superoxide anion concentration were observed in the offspring of diet-restricted dams. This study shows for the first time that intrauterine undernutrition enhances oxidative stress in vivo and relates this to the impaired endothelium-dependent vasodilation.