Vascular nitric oxide and superoxide anion contribute to sex-specific programmed cardiovascular physiology in mice

Robert D Roghair; Jeffrey L Segar; Kenneth A Volk; Mark W Chapleau; Lindsay M Dallas; Anna R Sorenson; Thomas D Scholz; Fred S Lamb

doi:10.1152/ajpregu.90756.2008

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Vascular nitric oxide and superoxide anion contribute to sex-specific programmed cardiovascular physiology in mice

Journal article

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Vascular nitric oxide and superoxide anion contribute to sex-specific programmed cardiovascular physiology in mice

Robert D Roghair, Jeffrey L Segar, Kenneth A Volk, Mark W Chapleau, Lindsay M Dallas, Anna R Sorenson, Thomas D Scholz and Fred S Lamb

American journal of physiology. Regulatory, integrative and comparative physiology, Vol.296(3), pp.R651-R662

03/2009

DOI: 10.1152/ajpregu.90756.2008

PMCID: PMC2665850

PMID: 19144750

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Abstract

Intrauterine environmental pertubations have been linked to the development of adult hypertension. We sought to evaluate the interrelated roles of sex, nitric oxide, and reactive oxygen species (ROS) in programmed cardiovascular disease. Programming was induced in mice by maternal dietary intervention (DI; partial substitution of protein with carbohydrates and fat) or carbenoxolone administration (CX, to increase fetal glucocorticoid exposure). Adult blood pressure and locomotor activity were recorded by radiotelemetry at baseline, after a week of high salt, and after a week of high salt plus nitric oxide synthase inhibition (by l -NAME). In male offspring, DI or CX programmed an elevation in blood pressure that was exacerbated by N ω -nitro- l -arginine methyl ester administration, but not high salt alone. Mesenteric resistance vessels from DI male offspring displayed impaired vasorelaxation to ACh and nitroprusside, which was blocked by catalase and superoxide dismutase. CX-exposed females were normotensive, while DI females had nitric oxide synthase-dependent hypotension and enhanced mesenteric dilation. Despite the disparate cardiovascular phenotypes, both male and female DI offspring displayed increases in locomotor activity and aortic superoxide production. Despite dissimilar blood pressures, DI and CX-exposed females had reductions in cardiac baroreflex sensitivity. In conclusion, both maternal malnutrition and fetal glucocorticoid exposure program increases in arterial pressure in male but not female offspring. While maternal DI increased both superoxide-mediated vasoconstriction and nitric oxide mediated vasodilation, the balance of these factors favored the development of hypertension in males and hypotension in females.

metabolic syndrome

intrauterine growth restriction

Developmental Physiology and Pregnancy

glucocorticoid

fetal origins of adult disease

Details

Title: Subtitle: Vascular nitric oxide and superoxide anion contribute to sex-specific programmed cardiovascular physiology in mice
Creators: Robert D Roghair - Departments of
Jeffrey L Segar - Departments of
Kenneth A Volk - Departments of
Mark W Chapleau - Departments of
Lindsay M Dallas - Departments of
Anna R Sorenson - Departments of
Thomas D Scholz - Departments of
Fred S Lamb - Departments of
Resource Type: Journal article
Publication Details: American journal of physiology. Regulatory, integrative and comparative physiology, Vol.296(3), pp.R651-R662
DOI: 10.1152/ajpregu.90756.2008
PMID: 19144750
PMCID: PMC2665850
NLM abbreviation: Am J Physiol Regul Integr Comp Physiol
ISSN: 0363-6119
eISSN: 1522-1490
Publisher: American Physiological Society
Language: English
Date published: 03/2009
Academic Unit: Molecular Physiology and Biophysics; Cardiology; Stead Family Department of Pediatrics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Child and Community Health; Neonatology; Internal Medicine
Record Identifier: 9984025457502771

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