title: Intrauterine growth restriction programs an accelerated age-related increase in cardiovascular risk in male offspring.
abstract: Placental insufficiency programs an increase in blood pressure associated with a twofold increase in serum testosterone in male growth-restricted offspring at 4 mo of age. Population studies indicate that the inverse relationship between birth weight and blood pressure is amplified with age. Thus, we tested the hypothesis that intrauterine growth restriction programs an age-related increase in blood pressure in male offspring. Growth-restricted offspring retained a significantly higher blood pressure at 12 but not at 18 mo of age compared with age-matched controls. Blood pressure was significantly increased in control offspring at 18 mo of age relative to control counterparts at 12 mo; however, blood pressure was not increased in growth-restricted at 18 mo relative to growth-restricted counterparts at 12 mo. Serum testosterone levels were not elevated in growth-restricted offspring relative to control at 12 mo of age. Thus, male growth-restricted offspring no longer exhibited a positive association between blood pressure and testosterone at 12 mo of age. Unlike hypertension in male growth-restricted offspring at 4 mo of age, inhibition of the renin-angiotensin system with enalapril (250 mg/l for 2 wk) did not abolish the difference in blood pressure in growth-restricted offspring relative to control counterparts at 12 mo of age. Therefore, these data suggest that intrauterine growth restriction programs an accelerated age-related increase in blood pressure in growth-restricted offspring. Furthermore, this study suggests that the etiology of increased blood pressure in male growth-restricted offspring at 12 mo of age differs from that at 4 mo of age.
authors.affiliation: Department of Physiology, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: John Henry
authors.initials: JH
authors.lastname: Dasinger
authors.affiliation: Department of Physiology, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Suttira
authors.initials: S
authors.lastname: Intapad
authors.affiliation: Department of Physiology, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Miles A
authors.initials: MA
authors.lastname: Backstrom
authors.affiliation: Department of Physiology, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Carter
authors.affiliation: Department of Physiology, University of Mississippi Medical Center, Jackson, Mississippi balexander@umc.edu.
authors.forename: Barbara T
authors.initials: BT
authors.lastname: Alexander
mesh_terms: D000375:Aging; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D001724:Birth Weight; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology*; D004656:Enalapril / Q000627:therapeutic use; D005260:Female; D005317:Fetal Growth Retardation / Q000473:pathology*; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology; D008297:Male; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects; D012307:Risk Factors; D013739:Testosterone / Q000097:blood
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D013739:Testosterone; D004656:Enalapril
keywords: accelerated aging; blood pressure; cardiovascular risk; low birth weight; renin-angiotensin system