The exaggerated salt-sensitive response in hypertensive transgenic rats (TGR mRen-2) fostered by a normotensive female

Suboptimal conditions during prenatal ontogeny can impair development of several physiological systems and result in cardiometabolic diseases in adulthood. The kidney has been identified as one of the most sensitive organs for developmental programming, but underlying mechanisms are not fully understood. Therefore, in our study we explored the consequences of prenatally increased angiotensin II (Ang II) on the structural development of the kidney and its damage by infiltrated immune cells under normal diet and after an increased salt intake, as a second insult representing a lifestyle factor in humans. Female rats were implanted with osmotic mini-pumps continuously releasing Ang II of dose 2 µg/kg/h during last two weeks of pregnancy, whereas control females were sham operated. Immunohistological and ultrastructural evaluations of the kidneys and their infiltration with immune cells were performed in mature male progeny kept either on a standard or increased salt (2% NaCl) diet. Glomerular volume decreased and the cortical tubulointerstitial injury increased in the offspring prenatally exposed to Ang II with no additional effect of increased salt. Ultrastructural examination demonstrated degenerative changes in proximal tubules, mainly fewer and shorter microvilli in the brush border, enlarged mitochondria, and an increased number of lysosomes in the epithelial cells in the progeny prenatally exposed to Ang II. Moreover, the treatment resulted in increased infiltration of T-cells and macrophages in the renal cortex compared to controls. These changes paralleled with reduced numbers of cytotoxic T-cells in circulation and higher oxidative burst of neutrophils in the progeny of Ang II-treated mothers compared to controls. Altogether, results suggest that prenatally increased Ang II promoted infiltration of immune cells in the kidney and subsequent oxidative stress, which induced a damage of renal glomerular and tubular system entailing negative consequences on the cardiovascular system. Impact statement Suboptimal prenatal conditions can contribute to development of cardiovascular diseases and an altered renin-angiotensin-aldosterone system (RAAS) can be involved in the process. In our study, increased angiotensin II in pregnant female rats resulted in renal cortical interstitial damage, and renal ultrastructural changes in the glomeruli, the brush border of proximal tubules and mitochondria in mature male offspring. The treatment promoted infiltration of T cells and macrophages in the kidneys and primed an oxidative burst of circulating neutrophils, indicating a pro-inflammatory state in the progeny of angiotensin II-treated mothers. Deregulated RAAS of mothers is involved in developmental programming of hypertension in adult male offspring via damaging kidney morphology and function. These findings suggest that preventing the activation of RAAS and oxidative stress during perinatal development might protect against hypertension development in adult male progeny.

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“…34 Moreover, Ang II is known to increase glomerular damage in models with genetic up-regulation of RAAS, such as TGR(mRen2)27 rats. 35…”

Section: Discussionmentioning

confidence: 99%

Renal impairment induced by prenatal exposure to angiotensin II in male rat offspring

Svitok

Okuliarova

Varga

et al. 2019

Exp Biol Med (Maywood)

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“…27 PH leads to endothelial dysfunction in systemic resistance arteries and affects the acute regulation of BP, 5,28 while chronic regulation of BP is mediated by the kidney. Prenatal adverse condition reduces foetal kidney growth and reduces the number of nephrons 5 and glomeruli, 29 an alteration that is often associated with later development of hypertension. 5 It leads in the kidney to upregulation of renin-angiotensin-aldosterone system.…”

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confidence: 99%

Prenatal hypoxia increases blood pressure in male rat offspring and affects their response to artificial light at night

Šutovska

Molčan

Koprdova

et al. 2020

J Dev Orig Health Dis

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Prenatal hypoxia (PH) has negative consequences on the cardiovascular system in adulthood and can affect the responses to additional insults later in life. We explored the effects of PH imposed during embryonic day 20 (10.5% O2 for 12 h) on circadian rhythms of systolic blood pressure (BP) and heart rate (HR) in mature male rat offspring measured by telemetry. We evaluated: (1) stability of BP and HR changes after PH; (2) circadian variability of BP and HR after 2 and 5 weeks of exposure to artificial light at night (ALAN; 1–2 lx); and (3) response of BP and HR to norepinephrine. PH increased BP in the dark (134 ± 2 mmHg vs. control 127 ± 2 mmHg; p = 0.05) and marginally in the light (125 ± 1 mmHg vs. control 120 ± 2 mmHg) phase of the day but not HR. The effect of PH was highly repeatable between 21- and 27-week-old PH male offspring. Two weeks of ALAN decreased the circadian variability of HR (p < 0.05) and BP more in control than PH rats. After 5 weeks of ALAN, the circadian variability of HR and BP were damped compared to LD and did not differ between control and PH rats (p < 0.05). Responses of BP and HR to norepinephrine did not differ between control and PH rats. Hypoxia at the end of the embryonic period increases BP and affects the functioning of the cardiovascular system in mature male offspring. ALAN in adulthood decreased the circadian variability of cardiovascular parameters, more in control than PH rats.

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Design and Simulation of Removable Pavement Edge Climbing Electric Wheelchair for Elderly and Disabled Users

Phannil

Jettanasen

2023

Int. J. Control Autom. Syst.

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The exaggerated salt-sensitive response in hypertensive transgenic rats (TGR mRen-2) fostered by a normotensive female

Cited by 6 publications

References 42 publications

Renal impairment induced by prenatal exposure to angiotensin II in male rat offspring

Renal impairment induced by prenatal exposure to angiotensin II in male rat offspring

Prenatal hypoxia increases blood pressure in male rat offspring and affects their response to artificial light at night

Design and Simulation of Removable Pavement Edge Climbing Electric Wheelchair for Elderly and Disabled Users

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