Sex-specific programming of hypertension in offspring of late-gestation diabetic rats

Ragheed Katkhuda; Emily S Peterson; Robert D Roghair; Andrew W Norris; Thomas D Scholz; Jeffrey L Segar

doi:10.1038/pr.2012.93

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Sex-specific programming of hypertension in offspring of late-gestation diabetic rats

Journal article

Open access

Peer reviewed

Sex-specific programming of hypertension in offspring of late-gestation diabetic rats

Ragheed Katkhuda, Emily S Peterson, Robert D Roghair, Andrew W Norris, Thomas D Scholz and Jeffrey L Segar

Pediatric research, Vol.72(4), pp.352-361

10/2012

DOI: 10.1038/pr.2012.93

PMCID: PMC3607358

PMID: 22805998

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Abstract

The intrauterine environment strongly influences adult disease susceptibility. We used a rat model of third-trimester maternal diabetes to test the hypothesis that adult offspring exposed to hyperglycemia in utero display increased blood pressure and alterations in vascular responsiveness. Diabetes was induced by streptozotocin injection to pregnant rats on gestation day 13 (term 21 d) and partially controlled with insulin injections. Hemodynamic function was evaluated in 6-12-mo-old offspring. Male but not female offspring of diabetic mothers (ODM) had significantly increased blood pressure as compared with controls; heart rate (HR) was similar. For both sexes, HR baroreflex responses were similar as were in vivo hemodynamic responses to angiotensin II, nitric oxide synthase inhibition, and ganglionic blockade. Aortic contractility to angiotensin II was similar in the two groups. Nitric oxide synthase inhibition and the Cu/Zn superoxide dismutase inhibitor diethyldithiocarbamate, but not the superoxide dismutase-mimetic Tempol, significantly increased contractile responses to angiotensin II in controls but not ODM. Reduced nicotinamide adenine dinucleotide phosphate-stimulated superoxide production was greater in male ODM than in controls (P < 0.05). Exposure to hyperglycemia in utero results in sex-specific cardiovascular changes in adult offspring. Impaired nitric oxide-reactive oxygen species signaling may play a significant role in the hemodynamic phenotype of ODM.

Signal Transduction

Pregnancy

Phenotype

Age Factors

Diabetes, Gestational - metabolism

Streptozocin

Diabetes, Gestational - chemically induced

Nitric Oxide Synthase - antagonists & inhibitors

Superoxide Dismutase - antagonists & inhibitors

Male

Ganglionic Blockers - pharmacology

Vasodilation

Hypertension - etiology

Dose-Response Relationship, Drug

Diabetes, Gestational - physiopathology

Superoxides - metabolism

Female

Blood Pressure - drug effects

Diabetes Mellitus, Experimental - chemically induced

Diabetes Mellitus, Experimental - complications

Diabetes Mellitus, Experimental - metabolism

Superoxide Dismutase - metabolism

Diabetes Mellitus, Experimental - physiopathology

Vasoconstrictor Agents - pharmacology

Heart Rate

Angiotensin II - pharmacology

Vasodilator Agents - pharmacology

Enzyme Inhibitors - pharmacology

Vasoconstriction

Rats

Gestational Age

Rats, Sprague-Dawley

Hypertension - physiopathology

Hypertension - metabolism

Animals

Baroreflex

Sex Factors

Nitric Oxide Synthase - metabolism

Nitric Oxide - metabolism

Details

Title: Subtitle: Sex-specific programming of hypertension in offspring of late-gestation diabetic rats
Creators: Ragheed Katkhuda - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Emily S Peterson - University of Iowa
Robert D Roghair
Andrew W Norris
Thomas D Scholz
Jeffrey L Segar
Resource Type: Journal article
Publication Details: Pediatric research, Vol.72(4), pp.352-361
DOI: 10.1038/pr.2012.93
PMID: 22805998
PMCID: PMC3607358
NLM abbreviation: Pediatr Res
ISSN: 0031-3998
eISSN: 1530-0447
Grant note: R01 HL088883 / NHLBI NIH HHS R01 DK081548 / NIDDK NIH HHS R01 HL102659 / NHLBI NIH HHS DK077599 / NIDDK NIH HHS
Language: English
Date published: 10/2012
Academic Unit: Endocrinology and Diabetes; Cardiology; Stead Family Department of Pediatrics; Fraternal Order of Eagles Diabetes Research Center; Child and Community Health; Biochemistry and Molecular Biology; Neonatology
Record Identifier: 9984093362902771

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