Block BS, Schlafer DH, Wentworth RA, Kreitzer LA and Nathanielsz PW (1990) MA (1993)

A series of epidemiological studies have described a relationship between low birth weight and high blood pressure in adult life and have proposed that factors associated with restriction of growth in utero act to reprogramme the development of the cardiovascular system which leads to the emergence of hypertension in adult life (Barker et al. 1990; Barker, 1992). It has also been demonstrated in pregnant rats that maternal protein restriction results in high blood pressure in the growth restricted offspring (Langley & Jackson, 1994). Interestingly, in these experiments treatment of the offspring for a 3 week period with the angiotensin converting enzyme (ACE) inhibitor captopril normalized the blood pressure (Langley-Evans & Jackson, 1995). These studies in the postnatal rat provide clear evidence that the renin-angiotensin system is important in the maintenance of hypertension in the offspring after maternal nutrient restriction during pregnancy. It is unknown, however, whether growth restriction in utero is associated with changes in the role of the renin-angiotensin system in the regulation of arterial blood pressure before birth. A model of experimental restriction of placental growth and function which results in fetal hypoxaemia, hypoglycaemia and growth restriction has been previously described (Robinson et al. 1979(Robinson et al. , 1980).In the present study we have also investigated the effects of experimental restriction of placental growth and function, and hence fetal growth, on fetal arterial blood pressure during late gestation and we have infused captopril to determine the role of the endogenous renin-angiotensin system in the maintenance of blood pressure in the growth restricted fetus. We have also investigated the effects of placental restriction on the blood pressure responses of the growth restricted fetus to increasing doses of angiotensin II (AII). METHODS Animals and surgeryAll procedures were approved by The University of Adelaide Animal Ethics Committee. Thirty-three pregnant Border ² Leicester cross Merino ewes were used in this study. In 14 ewes (placental restriction group; PR), the majority of endometrial caruncles were removed from the uterus prior to conception as previously described (Robinson et al. 1979). This procedure restricts the number of placental cotyledons which are formed subsequently limiting placental and hence fetal growth (Robinson et al. 1979). All surgery was performed under aseptic conditions with general anaesthesia induced by an intravenous injection of sodium thiopentone (1•25 g ml¢, Boehringer Ingelheim, NSW, Australia) and

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We have investigated the impact of chronic restriction of placental function on circulating catecholamine concentrations and responses to the indirectly acting, sympathomimetic amine, tyramine, in the fetal sheep in late gestation. In 10 ewes, endometrial caruncles or placental placentation sites were removed before conception (placental restriction (PR) group). Fetal sheep in the PR group were hypoxemic throughout late gestation and growth-restricted (3.02 +/- 0.35 kg) when compared with control fetal sheep (4.30 +/- 0.29 kg; n = 8) at 140 d of gestation. Fetal plasma concentrations of noradrenaline and adrenaline were higher (p < 0.05) in the PR (7.06 +/- 3.17 pmol/mL and 2.89 +/- 2.01 pmol/mL, respectively) than in the control group (3.55 +/- 0.54 pmol/mL and 1.30 +/- 0.48 pmol/mL, respectively) throughout late gestation. Plasma noradrenaline, but not adrenaline concentrations, increased significantly between 110 and 140 d of gestation in both the PR and control group, and there was a significant inverse relationship between plasma noradrenaline and arterial PO2 in the PR and control groups (plasma noradrenaline = 12.34 - 0.40 PO2). In the PR group, plasma noradrenaline increased (p < 0.05) after tyramine infusion from 4.51 +/- 1.28 pmol/mL to a peak of 19.40 +/- 3.56 pmol/mL. In the control group, noradrenaline increased from 2.08 +/- 0.30 pmol/mL to a peak of 12.23 +/- 1.67 pmol/mL after tyramine infusion. There was no difference, however, in the maximal proportional changes in plasma noradrenaline concentrations in the PR (319 +/- 55%) and control (449 +/- 100%) groups after tyramine. We conclude that the most likely source of the increased plasma catecholamines in the PR group is enhanced catecholamine synthesis and secretion from developing sympathetic neurons.

Small size at birth has been associated with increased blood pressure in adult men and women. In rats, isocaloric protein restriction reduces fetal growth and increases systolic blood pressure in adult offspring. Balanced maternal undernutrition in the rat also increases adult blood pressure, but not consistently. The aim of this study was to determine the effect of moderate balanced maternal undernutrition (85% of ad libitum intake from 4 weeks before, and throughout pregnancy) on blood pressure of adult offspring in the guinea pig, a species that is relatively mature at birth. Blood pressure was measured in chronically cathetensed offspring of ad libitum fed or feed-restricted mothers, at 3 months of age (young adult). Maternal feed restriction reduced birth weight (-17%) and increased systolic blood pressure (+9%, P < 0.03) in young adult male offspring. In offspring of ad libitum fed and feed-restricted mothers, combined data showed that systolic blood pressure and mean arterial pressure correlated negatively with head width at birth (P = 0.02 and P = 0.04, respectively, n = 28). Systolic blood pressure also correlated negatively with birth weight and the ratio birth wei@t/birth length, but only in offspring of ad libitum fed mothers ( P = 0.04 and P = 0.03, respectively, n = 22). The effect of maternal feed restriction on systolic blood pressure in male offspring was not si@cant when adjusted for these measures of size at birth. Thus, moderate balanced undernutrition in the guinea pig increases systolic blood pressure in young adult male offspring; however, these effects may be mediated, at least in part, through effects on fetal growth.

SUMMARYThe effects of two different feeding regimes on the 24 h profiles of maternal and fetal plasma cortisol and adrenocorticotrophic hormone (ACTH) concentrations were studied in eight pregnant ewes between 123 and 144 days of gestation. Once daily-fed ewes (n = 4) received

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