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Vascular nitric oxide and superoxide anion contribute to sex-specific programmed cardiovascular physiology in mice. Am J Physiol Regul Integr Comp Physiol 2009 Mar;296(3):R651-62



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Scopus ID

2-s2.0-64149128615   35 Citations


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(omega)-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.

Author List

Roghair RD, Segar JL, Volk KA, Chapleau MW, Dallas LM, Sorenson AR, Scholz TD, Lamb FS


Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

11-beta-Hydroxysteroid Dehydrogenases
Blood Pressure
Blood Vessels
Cardiovascular Physiological Phenomena
Diet, Protein-Restricted
Dietary Carbohydrates
Fetal Nutrition Disorders
Mice, Inbred C57BL
Motor Activity
Nitric Oxide
Nitric Oxide Synthase
Reactive Oxygen Species
Sex Characteristics
Splanchnic Circulation
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0