Numerous epidemiological studies, together with mounting evidence from studies in animals, point to a correlation between an adverse intrauterine environment and the early onset of cardiovascular and metabolic diseases later in life. We were the first to show that sheep exposed to dexamethasone (0.28 mg.kg-1.day-1 for only 2 days) at the end of the first month of pregnancy (PTG1), but not those exposed at the end of the second month of pregnancy (PTG2), had a higher basal mean arterial pressure (MAP) 19 months after birth. In the present study we report the MAP, cardiovascular haemodynamics and baroreflex sensitivity in these animals at 40 months of age. MAP in the PTG1 group was significantly higher than in the control group (91+/-1 mmHg and 81+/-1 mmHg respectively; P<0.001) and also when compared with the PTG2 group (82+/-1 mmHg; P<0.001). There was a significant increase in cardiac output in the PTG1 group compared with the control group (108+/-2 and 96+/-4 ml.min-1.kg-1 respectively; P<0.05). The increase in cardiac output in the PTG1 group was due to an increase in stroke volume (1.82+/-0.08 ml.kg-1. beat-1, compared with 1.46+/-0.06 ml.kg-1.beat-1 in the control group; P<0.05), but not in heart rate. In the hypertensive group of animals (PTG1), there was a rightward shift of the baroreflex curve. In group PTG2 (the normotensive group of animals), a lower gain was found before and during propranolol treatment. The decrease in gain of the baroreflex was not associated with changes in heart rate range, suggesting an impairment in the central processing of the baroreceptor signals. Thus sheep fetuses exposed to dexamethasone for only 2 days at the end of the first month of gestation have high blood pressure (dependent upon the increase in cardiac output) and a reset of the baroreflex at 40 months of age. Animals that have received prenatal dexamethasone closer to mid-gestation, although normotensive with normal cardiac output, showed an altered baroreceptor-heart rate response.

Our results indicate that D allele or DD homozygous is associated with the ESRD susceptibility in DN patients. However, more investigations are required to further this association.

These findings indicate that Ca(2+) entry via the α(1A)-AR-Snapin-TRPC6-pathway plays an important role in physiological regulation of cardiac contractility and may be an important target for augmenting cardiac performance.

1. Experiments were carried out in 30 chronically catheterized foetal sheep (128-144 days; term 150 days) and in seven of these foetuses before, during and after acute hypoxaemia. The extent to which changes in sympathoadrenal activity and cardiac vagal activity affected the foetal cardiac response to hypoxaemia was measured. Three measurements were used: foetal heart rate (FHR), heart rate variability (HRV; measured as the coefficient of variation in pulse interval) and power spectral density (PSD; measured over the frequency ranges of 0.04-1.3 Hz). Cardiac vagal activity was blocked by atropine, beta-adrenoceptor activity was blocked by propranolol. 2. Under normoxaemic conditions, cardiac vagal blockade caused a rise in mean arterial pressure (MAP; P < 0.001), an increase in FHR (P < 0.001), a decrease in HRV (P < 0.001) and a decrease in PSD (P < 0.001). beta-adrenoceptor blockade caused a rise in MAP (P < 0.001), a fall in FHR (P < 0.01), a decrease in HRV (P < 0.001) but no change in PSD. 3. During mild hypoxaemia (PO2 = 12-14.5 mmHg) and moderate hypoxaemia (PO2 = 10-11.9 mmHg), foetal MAP (P < 0.001, P< 0.001), HRV (P < 0.01, P < 0.001) and PSD in the frequency range 0.04-0.45 Hz increased (P < 0.05-P < 0.001). Foetal heart rate decreased when foetuses became moderately hypoxaemic (P < 0.001). 4. After cardiac vagal blockade, hypoxaemia was associated with an increase in FHR compared with non-blocked hypoxaemic foetuses (P < 0.01, P < 0.001). The increase in HRV was abolished (P < 0.001, P < 0.001) as was the increase in PSD (P < 0.01-P < 0.001). 5. After beta-adrenoceptor blockade, the bradycardia that occurred during hypoxaemia was enhanced (P < 0.01, P < 0.05), the increase in HRV was not affected and neither was the increase in PSD. 6. As FHR and HRV of normoxaemic foetal sheep were affected both by atropine and propranolol, it would seem that both cardiac vagal and sympathoadrenal activity modulate the foetal heart under resting conditions. The lack of any effect of beta-adrenoceptor blockade on PSD under these conditions suggests that power spectral analysis (PSA) is not as sensitive as the other two methods in detecting sympathetically mediated modulation of the heart. 7. Because the hypoxaemia induced bradycardia and increase in HRV and in PSD were abolished by atropine (P < 0.01-P < 0.001), it is concluded that during hypoxaemia foetal HRV is mainly modulated by changes in cardiac vagal tone. Propranolol had no effect on foetal HRV, although it reduced it under normoxaemic conditions; therefore, it is concluded that cardiac sympathetic neural activity was not increased in acute hypoxaemia uncomplicated by acidosis. However, there was strong evidence of increased sympathoadrenal tone on the foetal heart in hypoxaemia, that is, there was a rise in FHR in hypoxaemic atropinized foetuses and a greater fall in FHR in beta-adrenoceptor blocked hypoxaemic foetuses. Therefore, this increased sympathetic influence on the foetal heart during hypoxaemia must be predominantly the result of increased adrenome...

1. Brain sparing is a feature of intra-uterine growth retardation (IUGR). This implies that there is a redistribution of metabolic supply so that body growth slows to a greater extent than brain growth. 2. Intra-uterine growth retardation, as evidenced by a low birthweight for gestational age is a predisposing factor for hypertension, cardiovascular disease and diabetes mellitus in adult life. 3. In species like humans, nephrogenesis is complete before birth. In the rat, it is completed shortly after birth. In both species, it can be shown that either undernutrition or IUGR is associated with reduced nephron number. 4. It has been proposed that oligonephropathy results in hyperfiltration, which ultimately leads to glomerulosclerosis and hypertension. The renin-angiotensin system (RAS) is necessary for normal renal development and fetal renal function. In the rat, blockade of the RAS in the first weeks of life by pharmacological agents reduces glomerular number and has been shown to cause hypertension in adult life. Renal denervation reduces the activity of the fetal RAS and also causes abnormal development of the renin-secreting cells. 5. There is tonic renal sympathetic nerve activity in the late gestation fetal sheep. The level of renal sympathetic nerve activity (RSNA) is influenced by the fetal behavioural state. 6. However, interactions between the developing kidney and the developing sympathetic nervous system are poorly understood. On the one hand, renal innervation may be important in the provision of neurotrophic factors that stimulate the development of the RAS and kidney. On the other, high levels of RSNA associated with circulating catecholamines and vasopressin may cause vasoconstriction and limit nephrogenesis. This latter effect could be a predisposing factor to adult hypertension and cardiovascular disease.