Effect of Maternal Nutrient Restriction in Early Gestation on Responses of the Hypothalamic‐Pituitary‐Adrenal Axis to Acute Isocapnic Hypoxaemia in Late Gestation Fetal Sheep

Abstract

Epidemiological and experimental evidence suggests that maternal undernutrition during pregnancy may alter development of fetal organ systems. We have demonstrated previously that fetal hypothalamicpituitary-adrenal (HPA) axis responses to exogenous corticotropin-releasing hormone (CRH) + arginine vasopressin (AVP), or adrenocorticotrophin hormone (ACTH), are reduced in fetuses of mildly undernourished ewes. To examine these effects further we tested HPA axis responses to acute isocapnic hypoxaemia in fetal sheep at 114-129 days gestation (dGA), following 15% reduction in maternal nutritional intake between 0 and 70 dGA. Fetuses from control (C) and nutrient-restricted (R) ewes were chronically catheterised and plasma ACTH and cortisol responses were determined at 114-115, 120-123 and 126-129 dGA during hypoxaemia (1 h) induced by lowering the maternal inspired Oµ fraction (FI,Oµ). Basal plasma cortisol concentrations and HPA axis responses at 114-115 and 120-123 dGA did not differ between C and R fetuses. At 126-129 dGA, both plasma ACTH (P < 0.01) and cortisol (P < 0.05) responses were smaller in R fetuses compared to C fetuses. Fetal blood gas status, fetal body weight, body proportions and organ weights did not differ between the groups. We conclude that mild maternal undernutrition alters development of the fetal HPA axis producing a reduction in pituitary and adrenal responsiveness to endogenous stimuli.

Malnutrition enhances cardiovascular responses to chemoreflex activation in awake rats

“…Nevertheless, mechanisms involved in the development of hypertensive states in malnourished animals should be explored further. A growing number of studies have suggested that the enhancement of sympathetic efferent activity could represent a risk factor for cardiovascular disease (Hawkins et al, 2000;Irigoyen et al, 2005;Young et al, 1985). We hypothesize that autonomic imbalance due to the low-protein diet could affect the sympathetic output to the heart and vessels and possibly contribute to the development of hypertension.…”

Maternal nutrition alters the expression of insulin-like growth factors in fetal sheep liver and skeletal muscle

“…For example, survival of lambs which are of normal birth weight and born by caesarean section following nutrient restriction between early to mid gestation can be reduced to 40% compared with 100% survival rates in lambs born to ewes adequately fed throughout pregnancy (Heasman et al 2000). Maternal nutrient restriction during early to mid gestation also reduces the fetal adrenocorticotrophin and cortisol response to isocapnic hypoxaemia in later gestation (Hawkins et al 2000). Furthermore, maternal undernutrition in late gestation results in enhanced neuropeptide Y mRNA abundance in the fetal hypothalamus near to term (Warnes et al 1998), again in the absence of any effect on fetal body or organ weight.…”

Baroreflex dysfunction in rats submitted to protein restriction

“…As glutamate seems to be the main neurotransmitter in most cases of synapses of the central baroreflex pathway (Talman et al, 1980), the changes in baroreflex parameters could possibly be ascribed to glutamate metabolism disturbance associated with the malnutrition state. Moreover, malnourishment induces direct and/or indirect changes in neurohumoral systems that affect blood pressure regulation (Bell and Slotkin, 1988;Benabe et al, 1993a,b;Benabe and Martinez-Maldonado, 1993;Fernandez-Repollet et al, 1987;Ferreira et al, 2003;Hawkins et al, 2000;Langley-Evans et al, 1996a;Mi et al, 2000). Another important mechanism is related to the production of insulin growth factors (IGF): IGFs are produced under growth hormone (GH) stimulation of the hepatic cells (Conchillo et al, 2007) and are found to be vasodilator via NO production (Begum et al, 1998;Cruzado et al, 2005;Nguyen et al, 2006;Vickers et al, 2001).…”

“…Malnourishment often produces marked impacts leading to multiple organ lesions, including cardiovascular disturbances (Fernandez-Repollet et al, 1987Hawkins et al, 2000;Oliveira et al, 2004). It also produces disturbances in the baroreflex sensitivity (Tropia et al, 2001).…”