PMID- 24864188
OWN - NLM
STAT- MEDLINE
DCOM- 20141228
LR  - 20211021
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2014
DP  - 2014
TI  - Melatonin therapy prevents programmed hypertension and nitric oxide deficiency in 
      offspring exposed to maternal caloric restriction.
PG  - 283180
LID - 10.1155/2014/283180 [doi]
LID - 283180
AB  - Nitric oxide (NO) deficiency is involved in the development of hypertension, a 
      condition that can originate early in life. We examined whether NO deficiency 
      contributed to programmed hypertension in offspring from mothers with 
      calorie-restricted diets and whether melatonin therapy prevented this process. We 
      examined 3-month-old male rat offspring from four maternal groups: untreated 
      controls, 50% calorie-restricted (CR) rats, controls treated with melatonin 
      (0.01% in drinking water), and CR rats treated with melatonin (CR + M). The 
      effect of melatonin on nephrogenesis was analyzed using next-generation 
      sequencing. The CR group developed hypertension associated with elevated plasma 
      asymmetric dimethylarginine (ADMA, a nitric oxide synthase inhibitor), decreased 
      L-arginine, decreased L-arginine-to-ADMA ratio (AAR), and decreased renal NO 
      production. Maternal melatonin treatment prevented these effects. Melatonin 
      prevented CR-induced renin and prorenin receptor expression. Renal 
      angiotensin-converting enzyme 2 protein levels in the M and CR + M groups were 
      also significantly increased by melatonin therapy. Maternal melatonin therapy had 
      long-term epigenetic effects on global gene expression in the kidneys of 
      offspring. Conclusively, we attributed these protective effects of melatonin on 
      CR-induced programmed hypertension to the reduction of plasma ADMA, restoration 
      of plasma AAR, increase of renal NO level, alteration of renin-angiotensin 
      system, and epigenetic changes in numerous genes.
FAU - Tain, You-Lin
AU  - Tain YL
AUID- ORCID: 0000-0002-7059-6407
AD  - Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and College of 
      Medicine, Chang Gung University, Kaohsiung 833, Taiwan ; Center for Translational 
      Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and 
      College of Medicine, Chang Gung University, Kaohsiung 833, Taiwan.
FAU - Huang, Li-Tung
AU  - Huang LT
AD  - Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and College of 
      Medicine, Chang Gung University, Kaohsiung 833, Taiwan ; Department of 
      Traditional Chinese Medicine, Chang Gung University, Linkou 333, Taiwan.
FAU - Hsu, Chien-Ning
AU  - Hsu CN
AD  - Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital and College of 
      Medicine, Chang Gung University, Kaohsiung 833, Taiwan ; Graduate Institute of 
      Clinical Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 
      833, Taiwan.
FAU - Lee, Chien-Te
AU  - Lee CT
AD  - Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung 
      Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung 833, 
      Taiwan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140422
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 63CV1GEK3Y (N,N-dimethylarginine)
RN  - 94ZLA3W45F (Arginine)
RN  - JL5DK93RCL (Melatonin)
SB  - IM
MH  - Animals
MH  - Arginine/analogs & derivatives/blood/metabolism
MH  - *Caloric Restriction
MH  - Female
MH  - Hypertension/diet therapy/*drug therapy
MH  - In Vitro Techniques
MH  - Kidney/drug effects/metabolism
MH  - Male
MH  - Melatonin/pharmacology/*therapeutic use
MH  - Nitric Oxide/*metabolism
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC4016897
EDAT- 2014/05/28 06:00
MHDA- 2014/12/30 06:00
PMCR- 2014/04/22
CRDT- 2014/05/28 06:00
PHST- 2014/01/06 00:00 [received]
PHST- 2014/03/18 00:00 [revised]
PHST- 2014/03/28 00:00 [accepted]
PHST- 2014/05/28 06:00 [entrez]
PHST- 2014/05/28 06:00 [pubmed]
PHST- 2014/12/30 06:00 [medline]
PHST- 2014/04/22 00:00 [pmc-release]
AID - 10.1155/2014/283180 [doi]
PST - ppublish
SO  - Oxid Med Cell Longev. 2014;2014:283180. doi: 10.1155/2014/283180. Epub 2014 Apr 
      22.