Vascular nitrosative stress in hypertension induced by fetal undernutrition in rats

TY - JOUR

T1 - Vascular nitrosative stress in hypertension induced by fetal undernutrition in rats

AU - Rodríguez-Rodríguez, Pilar

AU - Poasakate, Anuson

AU - Ruvira-Hernando, Santiago

AU - Gutierrez-Arzapalo, Perla Y

AU - Böger, Rainer

AU - Hannemann, Juliane

AU - Lüneburg, Nicole

AU - Arribas, Silvia M

N1 - © 2023. The Author(s).

PY - 2023/8

Y1 - 2023/8

N2 - 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.

AB - 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.

KW - Rats

KW - Animals

KW - Male

KW - Female

KW - Nitrosative Stress

KW - Acetylcholine

KW - Chromatography, Liquid

KW - NF-E2-Related Factor 2/metabolism

KW - Tandem Mass Spectrometry

KW - Hypertension/etiology

KW - Arginine

KW - Malnutrition/complications

KW - Nitric Oxide/metabolism

U2 - 10.1007/s13105-023-00949-1

DO - 10.1007/s13105-023-00949-1

M3 - SCORING: Journal article

C2 - 36821073

VL - 79

SP - 555

EP - 568

JO - J PHYSIOL BIOCHEM

JF - J PHYSIOL BIOCHEM

SN - 1138-7548

IS - 3

ER -