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Neonatal growth restriction-related leptin deficiency enhances leptin-triggered sympathetic activation and central angiotensin II receptor-dependent stress-evoked hypertension. Pediatr Res 2016 08;80(2):244-51

Date

04/07/2016

Pubmed ID

27049292

Pubmed Central ID

PMC4990468

DOI

10.1038/pr.2016.64

Scopus ID

2-s2.0-84983262241   3 Citations

Abstract

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‚ÄČng/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 RD

Author

Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Angiotensins
Animals
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
jenkins-FCD Prod-478 d1509cf07a111124a2d122fd3df854cc0b993c00