Maternal N-acetylcysteine therapy regulates hydrogen sulfide-generating pathway and prevents programmed hypertension in male offspring exposed to prenatal dexamethasone and postnatal high-fat diet.
Nitric Oxide
; 53: 6-12, 2016 Feb 29.
Article
em En
| MEDLINE
| ID: mdl-26743493
ABSTRACT
Nitric oxide (NO) and hydrogen sulfide (H2S) pathways are involved in the development of hypertension, a condition that can originate from early life. We examined whether asymmetric dimethylarginine (ADMA, a nitric oxide synthase inhibitor)/NO and H2S generating pathway contributed to programmed hypertension in offspring exposed to prenatal dexamethasone (DEX) and postnatal high-fat (HF) and whether N-acetylcysteine (NAC) therapy prevented this process. We examined 16-week-old male rat offspring from five groups control, DEX (0.1 mg/kg i.p. from gestational day 16-22), HF (58% high-fat diet from weaning to 4 months of age), DEX+HF, and NAC (1% in drinking water during lactation). Prenatal DEX and postnatal HF diet synergistically induced programmed hypertension in adult offspring, which was prevented by maternal NAC therapy. We attributed the protective effects of NAC on two-hit induced programmed hypertension to the reduction of plasma ADMA, restoration of plasma l-arginine-to-ADMA ratio, upregulation of gene expression of H2S-generating enzymes, restoration of renal 3-mercaptopyruvate sulphurtransferase (3MST) protein levels and activity, induction of plasma glutathione level, and reduction of oxidative stress. Manipulation of the ADMA-NO and H2S-generating pathways by maternal NAC therapy may be a potential approach to prevent programmed hypertension induced by two-hit insults.
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Base de dados:
MEDLINE
Assunto principal:
Efeitos Tardios da Exposição Pré-Natal
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Acetilcisteína
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Dieta Hiperlipídica
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Sulfeto de Hidrogênio
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Hipertensão
Limite:
Animals
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Pregnancy
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article