Placental insufficiency results in temporal alterations in the renin angiotensin system in male hypertensive growth restricted offspring

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2007-08, Vol.293 (2), p.R804-R811
• Main Authors: Grigore, Daniela, Ojeda, Norma B, Robertson, Elliot B, Dawson, Antoinette S, Huffman, Contrina A, Bourassa, Erick A, Speth, Robert C, Brosnihan, K. Bridget, Alexander, Barbara T
• Format: Article
• Language: English
• Subjects: ACE inhibitors; Angiotensinogen - genetics; Animals; Birth Weight; Blood pressure; Blood Pressure - physiology; Body Weight; Female; Hypertension; Hypertension - metabolism; Hypertension - physiopathology; Kidney - metabolism; Male; Peptidyl-Dipeptidase A - blood; Placental Insufficiency - metabolism; Placental Insufficiency - physiopathology; Pregnancy; Rats; Receptor, Angiotensin, Type 1 - metabolism; Renin - blood; Renin - genetics; Renin-Angiotensin System - physiology; Reproductive system; RNA, Messenger - metabolism; Rodents; Sex Factors
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00725.2006

1 Department of Physiology and the Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi; 2 Murrah High School, Jackson, Mississippi; 3 Department of Pharmacology, School of Pharmacy, University of Mississippi, University, Mississippi; and 4 The Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina Submitted 13 October 2006 ; accepted in final form 25 May 2007 Reduced uterine perfusion initiated in late gestation in the rat results in intrauterine growth restriction (IUGR) and development of hypertension by 4 wk of age. We hypothesize that the renin angiotensin system (RAS), a regulatory system important in the long-term control of blood pressure, may be programmed by placental insufficiency and may contribute to the etiology of IUGR hypertension. We previously reported that RAS blockade abolished hypertension in adult IUGR offspring; however, the mechanisms responsible for the early phase of hypertension are unresolved. Therefore, the purpose of this study was to examine RAS involvement in early programmed hypertension and to determine whether temporal changes in RAS expression are observed in IUGR offspring. Renal renin and angiotensinogen mRNA expression were significantly decreased at birth (80 and 60%, respectively); plasma and renal RAS did not differ in conjunction with hypertension (mean increase of 14 mmHg) in young IUGR offspring; however, hypertension (mean increase of 22 mmHg) in adult IUGR offspring was associated with marked increases in renal angiotensin-converting enzyme (ACE) activity (122%) and renal renin and angiotensinogen mRNA (7-fold and 7.4-fold, respectively), but no change in renal ANG II or angiotensin type 1 receptor. ACE inhibition (enalapril, 10 mg·kg –1 ·day –1 , administered from 2 to 4 wk of age) abolished hypertension in IUGR at 4 wk of age (decrease of 15 mmHg, respectively) with no significant depressor effect in control offspring. Therefore, temporal alterations in renal RAS are observed in IUGR offspring and may play a key role in the etiology of IUGR hypertension. intrauterine growth restriction; kidney; brain; angiotensin; rat Address for reprint requests and other correspondence: B. T. Alexander, Dept. of Physiology and Biophysics, Univ. of Mississippi Medical Center, 2500 North State St., Jackson, MS 39216-4505 (e-mail: balexander{at}physiology.umsmed.edu )