title: Long-term alteration in maternal blood pressure and renal function after pregnancy in normal and growth-restricted rats.
abstract: Intrauterine growth restriction is associated with increased risk of adult cardiorenal diseases. Small birth weight females are more likely to experience complications during their own pregnancy, including pregnancy-induced hypertension, preeclampsia, and gestational diabetes. We determined whether the physiological demand of pregnancy predisposes growth-restricted females to cardiovascular and renal dysfunction later in life. Late gestation bilateral uterine vessel ligation was performed in Wistar-Kyoto rats. At 4 months, restricted and control female offspring were mated with normal males and delivered naturally (ex-pregnant). Regardless of maternal birth weight, at 13 months, ex-pregnant females developed elevated mean arterial pressure (indwelling tail-artery catheter; +6 mm Hg), reduced effective renal blood flow ((14)C-PAH clearance; -23%), and increased renal vascular resistance (+27%) compared with age-matched virgins. Glomerular filtration rate ((3)H-inulin clearance) was not different across groups. This adverse cardiorenal phenotype in ex-pregnant females was associated with elevated systemic (+57%) and altered intrarenal components of the renin-angiotensin system. After pregnancy at 13 months, coronary flow (Langendorff preparation) was halved in restricted females compared with controls, and together with reduced NO excretion, this may increase susceptibility to additional lifestyle challenges. Our results have implications for aging females who have been pregnant, suggesting long-term cardiovascular and renal alterations, with additional consequences for females who were small at birth.
authors.affiliation: Department of Physiology, University of Melbourne, Parkville, Victoria 3010, Australia.   m.wlodek@unimelb.edu.au.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Gallo
authors.forename: Kate M
authors.initials: KM
authors.lastname: Denton
authors.forename: Karen M
authors.initials: KM
authors.lastname: Moritz
authors.forename: Marianne
authors.initials: M
authors.lastname: Tare
authors.forename: Helena C
authors.initials: HC
authors.lastname: Parkington
authors.forename: Meagan
authors.initials: M
authors.lastname: Davies
authors.forename: Melanie
authors.initials: M
authors.lastname: Tran
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Jefferies
authors.forename: Mary E
authors.initials: ME
authors.lastname: Wlodek
mesh_terms: D000804:Angiotensin II / Q000097:blood / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D005919:Glomerular Filtration Rate / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply / Q000503:physiopathology*; D008297:Male; D010927:Placental Insufficiency / Q000503:physiopathology; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000503:physiopathology; D051381:Rats; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000502:physiology; D012083:Renin / Q000097:blood / Q000378:metabolism; D013997:Time Factors; D014655:Vascular Resistance / Q000502:physiology
chemical_list: D000804:Angiotensin II; D012083:Renin