title: Neonatal growth restriction-related leptin deficiency enhances leptin-triggered sympathetic activation and central angiotensin II receptor-dependent stress-evoked hypertension.
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.
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, Iowa.
authors.forename: Veronica
authors.initials: V
authors.lastname: Peotta
authors.affiliation: Department of Pharmacology, University of Iowa, Iowa City, Iowa.|Department of Internal Medicine, University of Iowa, Iowa City, Iowa.
authors.forename: Kamal
authors.initials: K
authors.lastname: Rahmouni
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, Iowa.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Segar
authors.affiliation: Department of Pharmacology, University of Iowa, Iowa City, Iowa.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Morgan
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, Iowa.
authors.forename: Kate M
authors.initials: KM
authors.lastname: Pitz
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, Iowa.
authors.forename: Olivia M
authors.initials: OM
authors.lastname: Rice
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, Iowa.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Roghair
mesh_terms: D000809:Angiotensins / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004195:Disease Models, Animal; D006130:Growth Disorders / Q000097:blood* / Q000150:complications; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000503:physiopathology; D020738:Leptin / Q000097:blood* / Q000172:deficiency*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D011945:Receptors, Angiotensin / Q000097:blood*; D012084:Renin-Angiotensin System / Q000502:physiology; D015398:Signal Transduction; D013315:Stress, Psychological / Q000150:complications; D013564:Sympathetic Nervous System / Q000503:physiopathology*
chemical_list: D000809:Angiotensins; D020738:Leptin; D011945:Receptors, Angiotensin; D019808:Losartan