Developmental programming of cardiovascular disorders: focus on hypertension.
Increasing evidence suggests that adult cardiovascular disorders, e.g. hypertension, can be "programmed" in utero. The mechanisms that affect the developing fetus and lead to future cardiovascular disease are not fully established. This review addresses the possible involvement of maternal nutrition, sex steroids and other endocrine factors in the programming of hypertension in adulthood. Some possible mechanisms of subsequent development of hypertension in adulthood, such as elevated sympathetic and renin-angiotensin system activity, and failure of nephron development, also are discussed. Previous studies suggest that maternal undernutrition could be a major factor in fetal programming, but in light of the increased worldwide prevalence of obesity, maternal overnutrition is now receiving increased attention. Special emphasis is given here to this phenomenon. Obesity is associated with increased serum and tissue levels of proinflammatory cytokines, and loss of sensitivity to the adipokine leptin. It is postulated that this causes dysregulation of the hypothalamo-pituitary-adrenal axis, resulting in increased levels of circulating glucocorticoids. These factors could play a major role in programming, during the in utero period, of future hypertension in the offspring of obese mothers.
Department of Pharmacology and Toxicology, Michigan State University, E. Lansing, MI 48824, USA. mohankumrs@cvm.msu.edu
Sheba M J
SM
MohanKumar
Andrew
A
King
Andrew C
AC
Shin
Madhu P
MP
Sirivelu
P S
PS
MohanKumar
Gregory D
GD
Fink
D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005315:Fetal Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D044342:Malnutrition / Q000150:complications; D008954:Models, Biological; D009765:Obesity / Q000150:complications*; D011247:Pregnancy; D011248:Pregnancy Complications