Neonatal growth restriction-related leptin deficiency enhances leptin-triggered sympathetic activation and central angiotensin II receptor-dependent stress-evoked hypertension

Veronica Peotta; Kamal Rahmouni; Jeffrey L Segar; Donald A Morgan; Kate M Pitz; Olivia M Rice; Robert D Roghair

doi:10.1038/pr.2016.64

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Neonatal growth restriction-related leptin deficiency enhances leptin-triggered sympathetic activation and central angiotensin II receptor-dependent stress-evoked hypertension

Journal article

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Peer reviewed

Neonatal growth restriction-related leptin deficiency enhances leptin-triggered sympathetic activation and central angiotensin II receptor-dependent stress-evoked hypertension

Veronica Peotta, Kamal Rahmouni, Jeffrey L Segar, Donald A Morgan, Kate M Pitz, Olivia M Rice and Robert D Roghair

Pediatric research, Vol.80(2), pp.244-251

08/2016

DOI: 10.1038/pr.2016.64

PMCID: PMC4990468

PMID: 27049292

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Abstract

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. 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. 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. 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.

Receptors, Angiotensin - blood

Signal Transduction

Mice, Inbred C57BL

Losartan - pharmacology

Male

Renin-Angiotensin System - physiology

Random Allocation

Sympathetic Nervous System - physiopathology

Growth Disorders - blood

Hypertension - physiopathology

Hypertension - blood

Animals

Leptin - blood

Hypertension - complications

Angiotensins - metabolism

Blood Pressure - physiology

Mice

Leptin - deficiency

Stress, Psychological - complications

Disease Models, Animal

Growth Disorders - complications

Details

Title: Subtitle: Neonatal growth restriction-related leptin deficiency enhances leptin-triggered sympathetic activation and central angiotensin II receptor-dependent stress-evoked hypertension
Creators: Veronica Peotta - Department of Pediatrics, University of Iowa, Iowa City, Iowa
Kamal Rahmouni - Department of Internal Medicine, University of Iowa, Iowa City, Iowa
Jeffrey L Segar - Department of Pediatrics, University of Iowa, Iowa City, Iowa
Donald A Morgan - Department of Pharmacology, University of Iowa, Iowa City, Iowa
Kate M Pitz - Department of Pediatrics, University of Iowa, Iowa City, Iowa
Olivia M Rice - Department of Pediatrics, University of Iowa, Iowa City, Iowa
Robert D Roghair - Department of Pediatrics, University of Iowa, Iowa City, Iowa
Resource Type: Journal article
Publication Details: Pediatric research, Vol.80(2), pp.244-251
Publisher: United States
DOI: 10.1038/pr.2016.64
PMID: 27049292
PMCID: PMC4990468
ISSN: 0031-3998
eISSN: 1530-0447
Grant note: T35 HL007485 / NHLBI NIH HHS R01 HL102659 / NHLBI NIH HHS P01 HL084207 / NHLBI NIH HHS
Language: English
Date published: 08/2016
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Orthopedics and Rehabilitation; Neuroscience and Pharmacology; Neonatology; Internal Medicine
Record Identifier: 9984040282702771

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