Normal lactational environment restores nephron endowment and prevents hypertension after placental restriction in the rat.
Uteroplacental insufficiency in the rat restricts fetal growth, impairs mammary development, compromising postnatal growth; and increases adult BP. The roles of prenatal and postnatal nutritional restraint on later BP and nephron endowment in offspring from mothers that underwent bilateral uterine vessel ligation (restricted) on day 18 of pregnancy were examined. Sham surgery (control) and a group of rats with reduced litter size (reduced; litter size reduced at birth to five, equivalent to restricted group) were used as controls. Offspring (control, reduced, and restricted) were cross-fostered on postnatal day 1 onto a control (normal lactation) or restricted (impaired lactation) mother. BP in male offspring was determined by tail cuff at 8, 12, and 20 wk of age, with glomerular number and volume (Cavalieri/Physical Dissector method) and renal angiotensin II type 1 receptor (AT(1)R) mRNA expression (real-time PCR) determined at 6 mo. Restricted-on-restricted male offspring developed hypertension (+16 mmHg) by 20 wk together with a nephron deficit (-26%) and glomerular hypertrophy (P < 0.05). In contrast, providing a normal lactational environment to restricted offspring improved postnatal growth and prevented the nephron deficit and hypertension. Reduced-on-restricted pups that were born of normal weight but with impaired growth during lactation subsequently grew faster, developed hypertension (+16 mmHg), had increased AT(1A)R and AT(1B)R mRNA expression (P < 0.05), but had no nephron deficit. Our study identifies the prenatal and postnatal nutritional environments in the programming of adult hypertension, associated with distinct renal changes. It is shown for the first time that a prenatally induced nephron deficit can be restored by correcting growth restriction during lactation.
Wlodek
Mary E
ME
Department of Physiology, University of Melbourne, Parkville 3010, Australia. m.wlodek@unimelb.edu.au
Mibus
Amy
A
Tan
Adeline
A
Siebel
Andrew L
AL
Owens
Julie A
JA
Moritz
Karen M
KM
D000818:Animals; D000833:Animals, Suckling; D001724:Birth Weight; D001794:Blood Pressure; D005260:Female; D005317:Fetal Growth Retardation / Q000473:pathology* / Q000503:physiopathology; D006977:Hypertension, Renal / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D007678:Kidney Glomerulus / Q000002:abnormalities / Q000166:cytology / Q000502:physiology; D007774:Lactation; D008098:Litter Size; D008297:Male; D008892:Milk; D009399:Nephrons / Q000002:abnormalities* / Q000166:cytology / Q000502:physiology; D009929:Organ Size; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1