Antenatal antioxidant prevents adult hypertension, vascular dysfunction, and microvascular rarefaction associated with in utero exposure to a low-protein diet

Abstract

Nuyt AM. Antenatal antioxidant prevents adult hypertension, vascular dysfunction, and microvascular rarefaction associated with in utero exposure to a low-protein diet. Am J Physiol Regul Integr Comp Physiol 292: R1236 -R1245, 2007. First published November 30, 2006; doi:10.1152/ajpregu.00227.2006.-Developmental programming of hypertension is associated with vascular dysfunction characterized by impaired vasodilatation to nitric oxide, exaggerated vasoconstriction to ANG II, and microvascular rarefaction appearing in the neonatal period. Hypertensive adults have indices of increased oxidative stress, and newborns that were nutrient depleted during fetal life have decreased antioxidant defenses and increased susceptibility to oxidant injury. To test the hypothesis that oxidative stress participates in early life programming of hypertension, vascular dysfunction, and microvascular rarefaction associated with maternal protein deprivation, pregnant rats were fed a normal, low protein (LP), or LP plus lazaroid (lipid peroxidation inhibitor) isocaloric diet from the day of conception until delivery. Lazaroid administered along with the LP diet prevented blood pressure elevation, enhanced vasomotor response to ANG II, impaired vasodilatation to sodium nitroprusside, and microvascular rarefaction in adult offspring. Liver total glutathione was significantly decreased in LP fetuses, and kidney eight-isoprostaglandin F2␣ (8-isoPGF 2␣) levels were significantly increased in adult LP offspring; these modifications were prevented by lazaroid. Renal nitrotyrosine abundance and blood levels of 1,4-dihydroxynonene and 4-hydroxynonenal-protein adducts were not modified by antenatal diet exposure. This study shows in adult offspring of LP-fed dams prevention of hypertension, vascular dysfunction, microvascular rarefaction, and of an increase in indices of oxidative stress by the administration of lazaroid during gestation. Lazaroid also prevented the decrease in antioxidant glutathione levels in fetuses, suggesting an antenatal mild oxidative stress in offspring of LP-fed dams. These studies support the concept that perinatal oxidative insult can lead to permanent alterations in the cardiovascular system development.hypertension; vascular dysfunction; developmental origin of adult disease; oxidative stress; antioxidants.Cardiovascular diseases represent currently the leading cause of mortality in Western countries. The hypothesis of a developmental origin of these pathologies derives from epidemiological studies, indicating that, independent of genetic or life style factors, the risks of hypertension (HT), stroke, and coronary heart disease in later life are inversely proportional to birth weight. Alteration of the vascular response to ACh, a decreased arterial compliance, and an increased incidence of atherosclerosis are all evidence further illustrating the vascular risk in children and adults born with low birth weight and/or intrauterine growth retardation (3,4,44,47).Experimentally, HT is observed in adults after malnutrit...

Perinatal programming and cardiomyocyte aging

“…Это было подтверждено в экспериментах на кры-сах, получавших корм с низким содержанием бел-ка; их потомство имело артериальную гипертонию [71]. Добавление в пищу таким крысам антиокси-дантов (N-ацетилцистеина) предотвращало развитие гипертензии у потомства [71].…”

“…Добавление в пищу таким крысам антиокси-дантов (N-ацетилцистеина) предотвращало развитие гипертензии у потомства [71]. Напротив, добавле-ние в корм беременным крысам кортикостероидов (дексаметазона) увеличивало продукцию активных соединений кислорода [72].…”

Preterm Birth and Hypertension Risk

“…88 We have also shown that antioxidant supplementation in dams fed a low-protein diet prevents low glutathione levels, hypertension, and vascular dysfunction in the offspring. 109 These observations are particularly important considering that an oxidized redox state, oxidative stress, and low-grade inflammation all contribute to the pathogenesis of chronic disorders, such as hypertension, cardiovascular and kidney diseases, and type 2 diabetes mellitus 110,111 ; in this way, it is possible that these processes may enhance significantly the risk of chronic disease in neonates born preterm.…”

Hypercholesterolaemia, signs of islet microangiopathy and altered angiogenesis precede onset of type 2 diabetes in the Goto–Kakizaki (GK) rat

“…programming might strongly affect organ development and function [15][16][17] and GK rats present deficient beta cell mass from fetal life onwards [10,11]. Rat islet endothelial proliferation is very high around birth but declines rapidly during the first week postpartum [12].…”

“…Indeed, vessel development, a major component of pancreatic islet development and function, is particularly active around birth [12][13][14] and altered programming of vascularisation has been shown to affect the development and function of various organs [15][16][17].…”