Long-term effects of intrauterine malnutrition on vascular function in female offspring: implications of oxidative stress.
Maternal malnutrition is known to impair fetal growth and predispose to the development of hypertension and type 2 diabetes. Recently, studies have demonstrated that intrauterine malnutrition is followed later in male offspring by oxidative stress characterized by increased superoxide generation due to activation of NADPH oxidase and reduced antioxidant defenses. However, few studies have investigated the mechanisms involved in endothelial dysfunction in female offspring. We evaluated the effects of the exogenous application of superoxide scavengers on the endothelium-dependent vasorelaxation in the mesenteric microvessels of female offspring. In addition, we examined indicative parameters of oxidative stress by measuring superoxide anion concentration and the activity of superoxide dismutase (SOD) as a marker of antioxidant defenses. Pregnant female Wistar rats were fed either a normal diet or 50% of this, throughout gestation. Intrauterine malnutrition induced hypertension and increased superoxide production without affecting SOD activity. Topical application of MnTMPyP (SOD mimetic) and apocynin (NADPH oxidase inhibitor) significantly improved the altered arteriolar responses to acetylcholine and bradykinin. In addition, incubation with apocynin reduced superoxide generation in these female offspring. The data suggest that after exposure to intrauterine malnutrition, female offspring present an increased superoxide production that is, at least in part, responsible for an endothelial dysfunction observed in these animals. These effects may be mediated via modulation of enzyme systems that generate superoxide.
Franco
Maria C P
MC
Laboratory of Hypertension, Diabetes and Inflammation, Department of Pharmacology, Institute of Biomedical Sciences Av Prof Lineu Prestes, University of São Paulo, São Paulo, SP, Brazil.
Akamine
Eliana H
EH
Rebouças
Nancy
N
Carvalho
Maria Helena C
MH
Tostes
Rita C A
RC
Nigro
Dorothy
D
Fortes
Zuleica B
ZB
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005508:Food Deprivation / Q000502:physiology*; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D039382:Maternal Nutritional Physiological Phenomena / Q000502:physiology*; D008665:Metalloporphyrins / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D013152:Splanchnic Circulation / Q000187:drug effects / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D000098:Acetophenones; D008665:Metalloporphyrins; C502230:Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin; D014665:Vasodilator Agents; C056165:acetovanillone; D013482:Superoxide Dismutase