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Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Exposure to Sympathetic Stress during Gestation Modifies Cardiovascular and Metabolic Function in Female Progeny in Rats

Version 1 : Received: 18 June 2024 / Approved: 18 June 2024 / Online: 19 June 2024 (02:45:39 CEST)

How to cite: Piquer, B.; Paredes, A.; Alanis, C.; Peña, S.; Lara, H. E. Exposure to Sympathetic Stress during Gestation Modifies Cardiovascular and Metabolic Function in Female Progeny in Rats. Preprints 2024, 2024061234. https://doi.org/10.20944/preprints202406.1234.v1 Piquer, B.; Paredes, A.; Alanis, C.; Peña, S.; Lara, H. E. Exposure to Sympathetic Stress during Gestation Modifies Cardiovascular and Metabolic Function in Female Progeny in Rats. Preprints 2024, 2024061234. https://doi.org/10.20944/preprints202406.1234.v1

Abstract

Increased norepinephrine (NE) release from the sympathetic nerves during pregnancy in women or animal models, as occurs during stress, modifies the fetal environment and increases flow of NE to the fetus, programing the progeny and affecting its cardiovascular and metabolic function in adulthood. In the present work, gestating rats were exposed to stress during gestation and the female progeny was analyzed for heart and metabolic function. Pregnant Sprague–Dawley rats were exposed to cold stress (4 °C/3 h/day); rats’ female progeny were euthanized at 4, 20 and 60 days old and their hearts evaluated to determine the β-adrenergic receptor (βAR) mRNA, abundance and affinity to agonists and NE concentration. The in vivo response to glucose overload and the arterial pressure response to isoproterenol (ISO, 125 µg/kg weight/day/10 days) were monitored. Results: At 20 and 60 days old, stressed female progeny presented an increase in ventricular weight and no changes in the cardiac NE as compared with their age-matched controls. The β1AR mRNA in control rats decreased between 4 and 20 days of age, but stressed rats maintained 50% higher levels of mRNA as compared with their age-matched controls. This difference was also found in the protein abundance of β1AR. No differences were found at 60 days old. The β2AR mRNA levels were higher than in controls at both 4 and 20 days old, but not expressed in the amount of protein. An increase in the ratio of β1/β2 receptors was found at 20 days old but not at 60 days old. The displacement of 3H-dihydroalprenolol (DHA) from a membrane fraction with propranolol (β antagonist) showed decreased affinity (at 60 days old) but no changes in the βAR number. In vivo exposure to ISO induced a β-adrenergic overload and provoked death in 40% of stressed females by day 3 of ISO treatment. Regarding metabolic function, we found that stressed rats presented insulin resistance when adults. These data suggest permanent changes to the heart’s adrenergic response and metabolic function after rat progeny were stressed in the uterus.

Keywords

gestational programming; cardiovascular; norepinephrine; beta receptors

Subject

Medicine and Pharmacology, Endocrinology and Metabolism

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