title: The effects of pregnancy and maternal nutrition on the maternal renin-angiotensin system in sheep.
abstract: Physiological changes occurring in the mother during pregnancy can determine the outcome of pregnancy in terms of birthweight and neonatal viability. Maternal adaptations include plasma volume expansion linked to enhanced activity of the renin-angiotensin system (RAS). The present study was designed to determine whether these changes occur very early in gestation, and the extent to which maternal nutrient restriction may compromise the maternal RAS. Using sheep, we have investigated the effects of pregnancy per se, maternal nutrient restriction and later restoration of maternal diet on maternal body weight, plasma volume and plasma renin concentration (PRC), and angiotensinogen (Aogen) and arginine vasopressin (AVP) concentration. During the period of placental growth (i.e. 28-80 days gestation) ewes were fed either a nutrient-restricted (NR) diet or were well fed (WF). NR ewes consumed between 3.2 and 3.8 MJ day(-1) of metabolisable energy (ME) which is close to 60 % of requirements taking into account the ME required for both ewe maintenance and growth of the conceptus in order to produce a 4.5 kg lamb at term. WF ewes consumed 150 % of ME requirements. Restoration of maternal diet between 80 and 140 days gestation (i.e. fed to satiety and consuming between 8 and 10.9 MJ day(-1), which is close to 150 % of ME requirements) followed previous nutrient restriction. Between pre-conception and 28 days gestation, plasma volume increased in conjunction with a decline in PRC and Aogen concentration. During the period of nutrient restriction ewe body weight did not increase and plasma volume was lower in NR than WF ewes. During this time there was no effect of maternal nutrition on PRC; however, Aogen concentration was lower in the NR group. From 80 days gestation following the rise in food intake for previously NR ewes, greater increases in ewe body weight, plasma volume and PRC occurred up to term compared with ewes that were well fed throughout gestation. Plasma AVP concentration was not significantly affected by either maternal nutrition or gestational age. In conclusion, the stimulus of moderately severe maternal nutrient restriction evoked smaller rises in maternal weight, plasma volume and Aogen concentration than occurred in ewes that were well fed throughout gestation. Following the restoration of maternal diet after 80 days gestation, PRC gradually rose to peak at term. These adaptations in the maternal RAS during the critical period of placental growth may have long-term effects on fetal development.
authors.affiliation: Academic Division of Child Health, School of Human Development, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, UK.
authors.forename: J
authors.initials: J
authors.lastname: Dandrea
authors.forename: S
authors.initials: S
authors.lastname: Cooper
authors.forename: M M
authors.initials: MM
authors.lastname: Ramsay
authors.forename: M
authors.initials: M
authors.lastname: Keller-Woods
authors.forename: F
authors.initials: F
authors.lastname: Broughton Pipkin
authors.forename: M E
authors.initials: ME
authors.lastname: Symonds
authors.forename: T
authors.initials: T
authors.lastname: Stephenson
mesh_terms: D000808:Angiotensinogen / Q000097:blood; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D004906:Erythrocyte Count; D005260:Female; D005508:Food Deprivation / Q000502:physiology; D009747:Nutritional Physiological Phenomena / Q000502:physiology*; D010953:Plasma Volume / Q000187:drug effects; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology*; D012756:Sheep
chemical_list: D000808:Angiotensinogen; D001127:Arginine Vasopressin; D012083:Renin