title: Aliskiren Administration during Early Postnatal Life Sex-Specifically Alleviates Hypertension Programmed by Maternal High Fructose Consumption.
abstract: Key points summary Maternal high-fructose (HF) induces programmed hypertension in adult offspring.Early aliskiren administration prevents HF-induced hypertension in both sexes of adult offspring.HF regulates RAS components in the offspring kidney in a sex-specific manner.HF alters renal transcriptome, with female offspring being more sensitive.Deprogramming strategy to prevent hypertension might be sex-specific.
  
  
  BACKGROUND
  Maternal high fructose (HF) intake induced renal programming and hypertension in male adult offspring. We examined whether maternal HF intake causes programmed hypertension and whether aliskiren administration confers protection against the process in a sex-specific manner, with a focus on the transcriptome changes in the kidney using next-generation RNA sequencing (NGS) technology and renin-angiotensin system (RAS).
  
  
  METHODS
  Pregnant Sprague-Dawley rats received regular chow or chow supplemented with 60% fructose throughout pregnancy and lactation. Offspring were assigned to six groups: male control, male HF (MHF), MHF+Aliskiren, female control, female HF (FHF), and FHF+Aliskiren. Oral aliskiren 10 mg/kg/day was administered via gastric gavage between 2 and 4 weeks of age. Rats were sacrificed at 12 weeks of age.
  
  
  RESULTS
  Maternal HF intake induced programmed hypertension in 12-week-old offspring of both sexes. HF regulated renal transcriptome and RAS components in the offspring kidney in a sex-specific manner. Aliskiren administration prevented HF-induced programmed hypertension in both sexes of adult offspring. Aliskiren administration increased ACE2 and MAS protein levels in female kidneys exposed to maternal HF intake.
  
  
  CONCLUSIONS
  Maternal HF induced programmed hypertension in both sexes of adult offspring, which was sex-specifically mitigated by early aliskiren administration. Better understanding of the sex-dependent mechanisms that underlie maternal HF-induced renal programming will help develop a novel sex-specific strategy to prevent programmed hypertension.
authors.affiliation: Department of Pharmacy, Kaohsiung Chang Gung Memorial HospitalKaohsiung, Taiwan; School of Pharmacy, Kaohsiung Medical UniversityKaohsiung, Taiwan.
authors.forename: Chien-Ning
authors.initials: CN
authors.lastname: Hsu
authors.affiliation: Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan.
authors.forename: Kay L H
authors.initials: KL
authors.lastname: Wu
authors.affiliation: Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan.
authors.forename: Wei-Chia
authors.initials: WC
authors.lastname: Lee
authors.affiliation: Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan.
authors.forename: Steve
authors.initials: S
authors.lastname: Leu
authors.affiliation: Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan.
authors.forename: Julie Y H
authors.initials: JY
authors.lastname: Chan
authors.affiliation: Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineKaohsiung, Taiwan; Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineKaohsiung, Taiwan.
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Tain
keywords: aliskiren; fructose; hypertension; renin-angiotensin system; sex differences