Prenatal dexamethasone-induced programmed hypertension and renal programming

Sheen, Jiunn‐Ming; Yu, Hong‐Ren; Tiao, Mao‐Meng; Chen, Chih‐Cheng; Huang, Laura; Chang, Hsin-Yu; Tain, You‐Lin

doi:10.1016/j.lfs.2015.04.005

Cited by 40 publications

(43 citation statements)

References 31 publications

(72 reference statements)

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“…Our results demonstrated that there was a tendency for combined DEX and TCDD to cause a decrease in BW in adult offspring, despite not reaching statistical significance. Similar to our previous reports [6,7], prenatal DEX exposure had no effect on adult offspring’s BW. Whether combined DEX and TCDD exposure causes a negative effect on BW in adult offspring requires further evaluation.…”

Section: Discussionsupporting

confidence: 91%

“…To construct a prenatal DEX exposure model, dexamethasone (0.1 mg/kg body weight [BW]; Taiwan Biotech Co., Ltd., Taoyuan, Taiwan) or vehicle was intraperitoneally administered to pregnant SD rats from a gestational age of 16 to 22 days [6,7]. Additionally, pregnant dams received TCDD (200 ng/kg BW orally; Sigma-Aldrich, St. Louis, MO, USA) or corn oil vehicle (4 mL/kg BW) on gestational days 14 and 21 and postnatal days 7 and 14 to provide in utero and lactation exposure of pups to the dioxin, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…We previously reported that prenatal exposure to dexamethasone (DEX), a widely used synthetic glucocorticoid, induced programmed hypertension in adult offspring [6,7]. Glucocorticoids have been found to influence the metabolic pathway of TCDD [8].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Maternal Resveratrol Therapy Protects Male Rat Offspring against Programmed Hypertension Induced by TCDD and Dexamethasone Exposures: Is It Relevant to Aryl Hydrocarbon Receptor?

Hsu

Lin

et al. 2018

IJMS

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100

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Hypertension can originate from early-life adverse environmental in utero exposure to dexamethasone (DEX) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Since DEX and TCDD are related to the aryl hydrocarbon receptor (AHR) signaling pathway, we examined whether resveratrol, an AHR modulator and antioxidant, could prevent programmed hypertension via regulating AHR signaling and oxidative stress. Groups of four-month-old male rat offspring were studied (n = 7–8 per group): control, DEX (0.1 mg/kg i.p. from a gestational age of 16 to 22 days), TCDD (200 ng/kg in four once-weekly oral doses), DEX + TCDD, and DEX + TCDD + R (resveratrol 0.05% in drinking water throughout pregnancy and lactation). Maternal TCDD exposure aggravated prenatal DEX-induced hypertension in adult male offspring, which maternal resveratrol therapy prevented. Maternal TCDD exposure aggravated DEX-induced oxidative damage in offspring kidneys, which was prevented by resveratrol therapy. Maternal resveratrol therapy decreased asymmetric and symmetric dimethylarginine (ADMA and SDMA) levels, thereby preventing combined DEX and TCDD exposure-induced programmed hypertension. Increases in renal Ahrr and Cyp1a1 expression induced by DEX + TCDD exposure were restored by resveratrol therapy. The beneficial effects of resveratrol on DEX + TCDD-induced hypertension relate to reduced renal mRNA expression of Ren, Ace, and Agtr1a expression. Thus, the beneficial effects of resveratrol on DEX + TCDD-induced hypertension include reduction of oxidative stress, restoration of nitric oxide (NO) bioavailability, blockade of the renin–angiotensin system (RAS), and antagonizing AHR signaling pathway.

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Section: Discussionsupporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

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Maternal Resveratrol Therapy Protects Male Rat Offspring against Programmed Hypertension Induced by TCDD and Dexamethasone Exposures: Is It Relevant to Aryl Hydrocarbon Receptor?

Hsu

Lin

et al. 2018

IJMS

Self Cite

100

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“…However, animal studies have reported several adverse effects of prenatal steroid treatment on the development of central nervous system, endocrinal system, and immune system (Coe and Lubach 2005;Antonow-Schlorke et al 2009). Our results agree with these observations Yu et al 2014a;Lui et al 2015;Sheen et al 2015).…”

Section: Introductionsupporting

confidence: 93%

Age-Dependent Effects of Prenatal Dexamethasone Exposure on Immune Responses in Male Rats

Chou

Huang

Tain

et al. 2017

Tohoku J. Exp. Med.

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Prenatal glucocorticoid therapy is indicated in preterm delivery to prevent respiratory distress. This study was designed to evaluate the age-dependent effects of prenatal dexamethasone (DEX) therapy on the immune system using a rat model. Pregnant Sprague-Dawley rats received an intraperitoneal injection of DEX (0.1 mg/kg/day) or saline (VEH) over gestational days 14-20. Male offspring were sacrificed at postnatal day 7 (D7; infant stage), D120 (young adult stage), and D180 (adult stage) for evaluation of leukocyte subsets and isolation of splenocytes. The production of innate and adaptive immune cytokines was assessed from the culture supernatants of splenocytes, stimulated with lipopolysaccharide and concanavalin A, respectively. For innate cytokines, the levels of interferon gamma inducible protein 10 were significantly higher, but those of tumor necrosis factor-α were significantly lower, in the culture medium of splenocytes prepared from the DEX group at D120 than those in the VEH group. For adaptive cytokines, the levels of interleukin-4 (IL-4) were significantly higher at D7 and those of IL-10 were significantly higher at D120 after prenatal exposure to DEX. We also showed that the expression level of IL-4 mRNA was significantly higher in splenocytes prepared from the DEX group at D7, compared with the VEH group. Importantly, the mRNA expression level of T-bet, a key transcription factor for immune cells, was greatly decreased in the spleen of the DEX group at D7, compared with the VEH group. In conclusion, prenatal dexamethasone exposure shows the greater impact on immune responses of their male offspring in early life.

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“…In a model of rats treated with a GR agonist, the treatment blunted aortic prostacyclin production [30]. Regarding EDHF, in a rat model of prenatal dexamethasone exposure, GC was responsible for an imbalance between EDHF and EDCF production, to the detriment of EDHF in the aorta [31]. GCs are also responsible for increased sensibility to endothelium-derived vasoconstrictors, such as endothelin-1 [25, 32].…”

Section: Direct Effects Of Gcs On Endothelial Cells and Functionmentioning

confidence: 99%

Glucocorticoids and endothelial function in inflammatory diseases: focus on rheumatoid arthritis

et al. 2016

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Rheumatoid arthritis (RA) is the most common systemic autoimmune disease characterized by articular and extra-articular manifestations involving cardiovascular (CV) diseases. RA increases the CV mortality by up to 50 % compared with the global population and CV disease is the leading cause of death in patients with RA. There is growing evidence that RA favors accelerated atherogenesis secondary to endothelial dysfunction (ED) that occurs early in the course of the disease. ED is a functional and reversible alteration of endothelial cells, leading to a shift of the actions of the endothelium towards reduced vasodilation, proinflammatory state, proliferative and prothrombotic properties. The mechanistic links between RA and ED have not been fully explained, but growing evidence suggests a role for traditional CV factors, auto-antibodies, genetic factors, oxidative stress, inflammation and iatrogenic interventions such as glucocorticoids (GCs) use. GCs have been used in RA for several decades. Whilst their deleterious CV side effects were described in the 1950s, their effect on CV risk associated with inflammatory arthritis remains subject for debate. GC might induce negative effects on endothelial function, via a direct effect on endothelium or via increasing CV risk factors. Conversely, they might actually improve endothelial function by decreasing systemic and/or vascular inflammation. The present review summarizes the available data on the impact of GCs on endothelial function, both in normal and inflammatory conditions, with a special focus on RA patients.

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Prenatal dexamethasone-induced programmed hypertension and renal programming

Cited by 40 publications

References 31 publications

Maternal Resveratrol Therapy Protects Male Rat Offspring against Programmed Hypertension Induced by TCDD and Dexamethasone Exposures: Is It Relevant to Aryl Hydrocarbon Receptor?

Maternal Resveratrol Therapy Protects Male Rat Offspring against Programmed Hypertension Induced by TCDD and Dexamethasone Exposures: Is It Relevant to Aryl Hydrocarbon Receptor?

Age-Dependent Effects of Prenatal Dexamethasone Exposure on Immune Responses in Male Rats

Glucocorticoids and endothelial function in inflammatory diseases: focus on rheumatoid arthritis

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