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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?

1
Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
2
Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
3
Departments of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
4
Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(8), 2459; https://doi.org/10.3390/ijms19082459
Received: 20 July 2018 / Revised: 8 August 2018 / Accepted: 17 August 2018 / Published: 20 August 2018
(This article belongs to the Special Issue Aryl Hydrocarbon Receptor in Biology and Toxicology)
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. View Full-Text
Keywords: aryl hydrocarbon receptor; developmental origins of health and disease (DOHaD); hypertension; nitric oxide; oxidative stress; TCDD aryl hydrocarbon receptor; developmental origins of health and disease (DOHaD); hypertension; nitric oxide; oxidative stress; TCDD
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Hsu, C.-N.; Lin, Y.-J.; Lu, P.-C.; Tain, Y.-L. Maternal Resveratrol Therapy Protects Male Rat Offspring against Programmed Hypertension Induced by TCDD and Dexamethasone Exposures: Is It Relevant to Aryl Hydrocarbon Receptor? Int. J. Mol. Sci. 2018, 19, 2459.

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