Hawkins, Paul; (1999) Nutritional influences on development of the cardiovascular system and hypothalamic pituitary-adrenal axis. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Epidemiological evidence suggests that adult cardiovascular disease may originate in fetal life. In humans, impaired fetal development is associated with an increased incidence of hypertension and other cardiovascular disease risk factors. However, an adverse environmental influence during pregnancy may, if not severe, 'programme' fetal development to produce adaptations which preserve growth but have long-term effects on cardiovascular function. Experimental studies suggest that one such adverse environmental factor may be maternal nutrition, as restriction of maternal nutrient supply during pregnancy in rats produces hypertension in adult offspring. It is not known if these effects are initiated in fetal life. Furthermore, the mechanisms by which maternal undernutrition programmes fetal cardiovascular development are not fully understood. Experiments were performed to examine the effects of a modest level of maternal undernutrition in early gestation on fetal cardiovascular development in late gestation. Development of the fetal hypothalamic-pituitary-adrenal (HPA) axis, and fetal and placental growth were also examined to investigate the underlying mechanisms which may mediate changes in cardiovascular function. In addition, the physiological consequences of effects on the fetus were studied by investigating cardiovascular and HPA axis function in postnatal life. These experiments were conducted using chronic fetal and neonatal sheep preparations. The results of these studies show that fetuses of undernourished mothers have low mean arterial pressure (MAP) and reduced HPA axis activity. However, fetal body weight and body proportions are not altered. Reduced fetal HPA axis activity may be mediated by a decrease in corticotropin releasing hormone (CRH)-mediated stimulation of the pituitary gland. Postnatally, MAP is elevated and HPA axis activity is greater in offspring of nutritionally restricted mothers. Thus maternal undernutrition during pregnancy can programme fetal cardiovascular development without substantial effects on fetal growth or blood-gases. These alterations in cardiovascular development may be mediated by changes in activity of the HPA axis. Furthermore, development of postnatal hypertension may be initiated in utero, even though the mechanisms involved produce low blood pressure in fetal life.

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