Melatonin attenuates prenatal dexamethasone-induced blood pressure increase in a rat model

You Lin Tain, Chih Cheng Chen, Jiunn Ming Sheen, Hong Ren Yu, Mao Meng Tiao, Ho Chang Kuo, Li Tung Huang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

60 Scopus citations

Abstract

Although antenatal corticosteroid is recommended to accelerate fetal lung maturation, prenatal dexamethasone exposure results in hypertension in the adult offspring. Since melatonin is a potent antioxidant and has been known to regulate blood pressure, we examined the beneficial effects of melatonin therapy in preventing prenatal dexamethasone-induced programmed hypertension. Male offspring of Sprague-Dawley rats were assigned to four groups (n = 12/group): control, dexamethasone (DEX), control + melatonin, and DEX + melatonin. Pregnant rats received intraperitoneal dexamethasone (0.1 mg/kg) from gestational day 16 to 22. In the melatonin-treatment groups, rats received 0.01% melatonin in drinking water during their entire pregnancy and lactation. Blood pressure was measured by an indirect tail-cuff method. Gene expression and protein levels were analyzed by real-time quantitative polymerase chain reaction and Western blotting, respectively. At 16 weeks of age, the DEX group developed hypertension, which was partly reversed by maternal melatonin therapy. Reduced nephron numbers due to prenatal dexamethasone exposure were prevented by melatonin therapy. Renal superoxide and NO levels were similar in all groups. Prenatal dexamethasone exposure led to increased mRNA expression of renin and prorenin receptor and up-regulated histone deacetylase (HDAC)-1 expression in the kidneys of 4-month-old offspring. Maternal melatonin therapy augmented renal Mas protein levels in DEX + melatonin group, and increased renal mRNA expression of HDAC-1, HDAC-2, and HDAC-8 in control and DEX offspring. Melatonin attenuated prenatal DEX-induced hypertension by restoring nephron numbers, altering RAS components, and modulating HDACs.

Original languageEnglish
Pages (from-to)216-226
Number of pages11
JournalJournal of the American Society of Hypertension
Volume8
Issue number4
DOIs
StatePublished - 04 2014

Keywords

  • Asymmetric dimethylarginine
  • histone deacetylase
  • hypertension
  • melatonin
  • oxidative stress
  • renin-angiotensin system

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