Kidney angiotensin and angiotensin receptor expression in prenatally programmed hypertension.
Adult hypertension may be programmed by the prenatal environment in humans and in experimental animals. The potential role of the intrarenal renin-angiotensin system (RAS) in prenatally programmed hypertension was investigated. Hypertension in rat offspring was induced by maternal protein restriction during pregnancy. The offspring were studied on day 1 of life and immediately preceding the development of hypertension on day 28. ANG I and II contents were determined by radioimmunoassy. Angiotensin receptor protein and mRNA levels were quantified by immunoblotting and real-time RT-PCR, respectively. Plasma and kidney ANG I and II were unchanged in the offspring from low-protein pregnancies (LP). ANG II type 1 receptor (AT(1)R) protein abundance was low in the newborn LP kidney (P < 0.05) but rose above control values by 28 days of age (P < 0.05); the rise was associated with an increase in AT(1)R subtype A (P < 0.01), but not subtype B, mRNA level. ANG II type 2 receptor protein expression was decreased on day 1 (P < 0.05) and increased on day 28 (P < 0.05) in LP kidneys. The results show that prenatal programming of hypertension is associated with an abnormal pattern of intrarenal RAS ontogeny that may play a pathogenetic role, for instance, by constitutively altering renal hemodynamics or Na reabsorption.
Vehaskari
V Matti
VM
The Research Institute for Children, 200 Henry Clay Ave., New Orleans, LA 70118, USA. vvehas@lsuhsc.edu
Stewart
Tyrus
T
Lafont
Derek
D
Soyez
Christopher
C
Seth
Dale
D
Manning
Jennifer
J
D000375:Aging / Q000378:metabolism; D000809:Angiotensins / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D018753:Diet, Protein-Restricted; D005260:Female; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism*
D000809:Angiotensins; D020033:Protein Isoforms; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin