Vascular nitrosative stress in hypertension induced by fetal undernutrition in rats
Entity
UAM. Departamento de FisiologíaPublisher
SpringerDate
2023-02-23Citation
10.1007/s13105-023-00949-1
Journal of Physiology and Biochemistry (2023): 1-14
ISSN
1138-7548 (print); 1877-8755 (online)DOI
10.1007/s13105-023-00949-1Funded by
Open Access funding provided thanks to the CRUE-CSIC agreement with Springer NatureProject
Gobierno de España. RTI2018-097504-B-I00Editor's Version
https://doi.org/ 10.1007/s13105-023-00949-1Subjects
ADMA; Fetal programing; Nitric oxide; Nitrosative stress; Nrf2; MedicinaRights
© The Author(s) 2023Abstract
Fetal undernutrition predisposes to hypertension development. Since nitric oxide (NO) is a key factor in blood pressure control, we aimed to investigate the role of NO alterations in hypertension induced by fetal undernutrition in rats. Male and female offspring from dams exposed to undernutrition during the second half of gestation (MUN) were studied at 21 days (normotensive) and 6 months of age (hypertension developed only in males). In aorta, we analyzed total and phosphorylated endothelial NO synthase (eNOS, p-eNOS), 3-nitrotyrosine (3-NT), and Nrf2 (Western blot). In plasma we assessed l-arginine, asymmetric and symmetric dimethylarginine (ADMA, SDMA; LC–MS/MS), nitrates (NOx, Griess reaction), carbonyl groups, and lipid peroxidation (spectrophotometry). In iliac arteries, we studied superoxide anion production (DHE staining, confocal microscopy) and vasodilatation to acetylcholine (isometric tension). Twenty-one-day-old MUN offspring did not show alterations in vascular e-NOS or 3NT expression, plasma l-Arg/ADMA ratio, or NOx. Compared to control group, 6-month-old MUN rats showed increased aortic expression of p-eNOS/eNOS and 3-NT, being Nrf2 expression lower, elevated plasma l-arginine/ADMA, NOx and carbonyl levels, increased iliac artery DHE staining and reduced acetylcholine-mediated relaxations. These alterations in MUN rats were sex-dependent, affecting males. However, females showed some signs of endothelial dysfunction. We conclude that increased NO production in the context of a pro-oxidative environment, leads to vascular nitrosative damage and dysfunction, which can participate in hypertension development in MUN males. Females show a better adaptation, but signs of endothelial dysfunction, which can explain hypertension in ageing
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Google Scholar:Rodríguez Rodríguez, Pilar
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Poasakate, Anuson
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Ruvira Hernando, Santiago
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Gutierrez Arzapalo, Perla Y.
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Böger, Rainer
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Hannemann, Juliane
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Lüneburg, Nicole
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Arribas Rodríguez, Silvia Magdalena
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