Sex-specific differences in the mechanisms for enhanced thromboxane A 2 -mediated vasoconstriction in adult offspring exposed to prenatal hypoxia.

Autor:	Graton ME; Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB, T6G 2R3, Canada.; Women and Children's Health Research Institute, University of Alberta, Edmonton, AB, T6G 2R3, Canada., Spaans F; Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB, T6G 2R3, Canada.; Women and Children's Health Research Institute, University of Alberta, Edmonton, AB, T6G 2R3, Canada., He R; Women and Children's Health Research Institute, University of Alberta, Edmonton, AB, T6G 2R3, Canada.; Department of Physiology, University of Alberta, Edmonton, AB, T6G 2R3, Canada., Chatterjee P; Women and Children's Health Research Institute, University of Alberta, Edmonton, AB, T6G 2R3, Canada.; Department of Physiology, University of Alberta, Edmonton, AB, T6G 2R3, Canada., Kirschenman R; Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB, T6G 2R3, Canada.; Women and Children's Health Research Institute, University of Alberta, Edmonton, AB, T6G 2R3, Canada., Quon A; Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB, T6G 2R3, Canada.; Women and Children's Health Research Institute, University of Alberta, Edmonton, AB, T6G 2R3, Canada., Phillips TJ; UK Dementia Research Institute, Cardiff University, Cardiff, W1T 7NF, UK., Case CP; Musculoskeletal Research Unit, University of Bristol, Bristol, BS8 1QU, UK., Davidge ST; Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB, T6G 2R3, Canada. sandra.davidge@ualberta.ca.; Women and Children's Health Research Institute, University of Alberta, Edmonton, AB, T6G 2R3, Canada. sandra.davidge@ualberta.ca.
Jazyk:	angličtina
Zdroj:	Biology of sex differences [Biol Sex Differ] 2024 Jun 19; Vol. 15 (1), pp. 52. Date of Electronic Publication: 2024 Jun 19.
DOI:	10.1186/s13293-024-00627-x
Abstrakt:	Background: Prenatal hypoxia, a common pregnancy complication, leads to impaired cardiovascular outcomes in the adult offspring. It results in impaired vasodilation in coronary and mesenteric arteries of the adult offspring, due to reduced nitric oxide (NO). Thromboxane A 2 (TxA 2 ) is a potent vasoconstrictor increased in cardiovascular diseases, but its role in the impact of prenatal hypoxia is unknown. To prevent the risk of cardiovascular disease by prenatal hypoxia, we have tested a maternal treatment using a nanoparticle-encapsulated mitochondrial antioxidant (nMitoQ). We hypothesized that prenatal hypoxia enhances vascular TxA 2 responses in the adult offspring, due to decreased NO modulation, and that this might be prevented by maternal nMitoQ treatment. Methods: Pregnant Sprague-Dawley rats received a single intravenous injection (100 µL) of vehicle (saline) or nMitoQ (125 µmol/L) on gestational day (GD)15 and were exposed to normoxia (21% O 2 ) or hypoxia (11% O 2 ) from GD15 to GD21 (term = 22 days). Coronary and mesenteric arteries were isolated from the 4-month-old female and male offspring, and vasoconstriction responses to U46619 (TxA 2 analog) were evaluated using wire myography. In mesenteric arteries, L-NAME (pan-NO synthase (NOS) inhibitor) was used to assess NO modulation. Mesenteric artery endothelial (e)NOS, and TxA 2 receptor expression, superoxide, and 3-nitrotyrosine levels were assessed by immunofluorescence. Results: Prenatal hypoxia resulted in increased U46619 responsiveness in coronary and mesenteric arteries of the female offspring, and to a lesser extent in the male offspring, which was prevented by nMitoQ. In females, there was a reduced impact of L-NAME in mesenteric arteries of the prenatal hypoxia saline-treated females, and reduced 3-nitrotyrosine levels. In males, L-NAME increased U46619 responses in mesenteric artery to a similar extent, but TxA 2 receptor expression was increased by prenatal hypoxia. There were no changes in eNOS or superoxide levels. Conclusions: Prenatal hypoxia increased TxA 2 vasoconstrictor capacity in the adult offspring in a sex-specific manner, via reduced NO modulation in females and increased TP expression in males. Maternal placental antioxidant treatment prevented the impact of prenatal hypoxia. These findings increase our understanding of how complicated pregnancies can lead to a sex difference in the programming of cardiovascular disease in the adult offspring. (© 2024. The Author(s).)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.