Neonatal growth restriction-related leptin deficiency enhances leptin-triggered sympathetic activation and central angiotensin II receptor-dependent stress-evoked hypertension. Pediatr Res 2016 Aug;80(2):244-51
Date
04/07/2016Pubmed ID
27049292Pubmed Central ID
PMC4990468DOI
10.1038/pr.2016.64Scopus ID
2-s2.0-84983262241 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
BACKGROUND: Neonatal growth restriction (nGR) leads to leptin deficiency and increases the risk of hypertension. Previous studies have shown nGR-related hypertension is normalized by neonatal leptin (nLep) and exacerbated by psychological stress. With recent studies linking leptin and angiotensin signaling, we hypothesized that nGR-induced nLep deficiency increases adult leptin sensitivity; leading to leptin- or stress-induced hypertension, through a pathway involving central angiotensin II type 1 receptors.
METHODS: We randomized mice with incipient nGR, by virtue of their presence in large litters, to vehicle or physiologic nLep supplementation (80 ng/g/d). Adult caloric intake and arterial pressure were monitored at baseline, during intracerebroventricular losartan infusion and during systemic leptin administration.
RESULTS: nGR increased leptin-triggered renal sympathetic activation and hypertension with increased leptin receptor expression in the arcuate nucleus of the hypothalamus; all of those nGR-associated phenotypes were normalized by nLep. nGR mice also had stress-related hyperphagia and hypertension, but only the stress hypertension was blocked by central losartan infusion.
CONCLUSION: nGR leads to stress hypertension through a pathway that involves central angiotensin II receptors, and nGR-associated leptin deficiency increases leptin-triggered hypertension in adulthood. These data suggest potential roles for preservation of neonatal growth and nLep supplementation in the prevention of nGR-related hypertension.
Author List
Peotta V, Rahmouni K, Segar JL, Morgan DA, Pitz KM, Rice OM, Roghair RDAuthor
Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AngiotensinsAnimals
Blood Pressure
Disease Models, Animal
Growth Disorders
Hypertension
Leptin
Losartan
Male
Mice
Mice, Inbred C57BL
Random Allocation
Receptors, Angiotensin
Renin-Angiotensin System
Signal Transduction
Stress, Psychological
Sympathetic Nervous System
