Sex-specific programming of hypertension in offspring of late-gestation diabetic rats. Pediatr Res 2012 Oct;72(4):352-61
Date
07/19/2012Pubmed ID
22805998Pubmed Central ID
PMC3607358DOI
10.1038/pr.2012.93Scopus ID
2-s2.0-84867047874 (requires institutional sign-in at Scopus site) 35 CitationsAbstract
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSION: 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.
Author List
Katkhuda R, Peterson ES, Roghair RD, Norris AW, Scholz TD, Segar JLAuthor
Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Age FactorsAngiotensin II
Animals
Baroreflex
Blood Pressure
Diabetes Mellitus, Experimental
Diabetes, Gestational
Dose-Response Relationship, Drug
Enzyme Inhibitors
Female
Ganglionic Blockers
Gestational Age
Heart Rate
Hypertension
Male
Nitric Oxide
Nitric Oxide Synthase
Phenotype
Pregnancy
Rats
Rats, Sprague-Dawley
Sex Factors
Signal Transduction
Streptozocin
Superoxide Dismutase
Superoxides
Vasoconstriction
Vasoconstrictor Agents
Vasodilation
Vasodilator Agents
