K. Tangalakis

Effect of cortisol on blood pressure and vascular reactivity in the ovine fetus

The aim of this study was to investigate the cardiovascular effects of exogenous cortisol in fetal sheep, (a) between 100 and 120 days of gestation when cortisol production is minimal and (b) after 130 days when endogenous plasma cortisol starts to rise. Chronically cannulated ovine fetuses (103–120 days, n = 9; 130–137 days, n = 7), received sequentially a 24 h infusion of vehicle (0.9% sodium chloride) and a 24 h infusion of cortisol at 100 micrograms/h. Blood pressure and heart rate changes to bolus injections each of angiotensin II and noradrenaline (0.2, 0.5, 1.0, 2.0 micrograms) were measured before and after the saline and cortisol infusions. Fetuses in each age group, served as additional controls receiving 48 h saline infusions. In both immature and mature age groups, the cortisol infusion increased basal fetal blood cortisol concentrations by 33.7 and 35.4 nmol/l respectively. In the immature group, cortisol, but not saline, caused significant 14.3 and 15.3% increases in basal systolic and diastolic pressures respectively. Basal blood pressure was higher in the mature group, but did not increase further despite the increase in cortisol levels. Furthermore, vascular responsiveness to angiotensin II but not to noradrenaline was significantly enhanced following the cortisol infusion, at both ages. Fetal heart rate did not change following the cortisol infusion. Exogenous cortisol contributes to the regulation of fetal blood pressure in the immature fetus, when other mechanisms have not developed. Cortisol might achieve this, in part, by enhancing vascular sensitivity to angiotensin II.

Experimental hydranencephaly in the ovine fetus

Abstract Hydranencephaly is defined as the replacement of a previously normal brain, in whole or in part, by membranous fluid-filled sacs. The etiology is not well understood, and the time course of development is unknown. Fifteen ovine fetuses were chronically cannulated and had both carotid arteries ligated at 100 days of gestation (term is 145–150 days). They were killed at 1 (n = 4), 2 (n = 6) and 4 (n = 5) weeks post-surgery, and the findings compared with those of 25 age-matched controls. By 2 weeks post-surgery the entire cerebral hemispheres and diencephalon had been replaced by fluid closely resembling cerebrospinal fluid. The choroid plexus, pituitary and brain stem remained outwardly normal, but the cerebellum showed signs of damage. Fetuses maintained normal values for blood gases and hematocrit up to 4 weeks post-surgery, and grew normally. Light microscopy of the brain stem showed significant losses of cell populations in the medulla by 4 weeks. Vascular casting and acute blood flow studies in an additional group of fetuses showed that the entire brain was perfused via the vertebral-occipital anastomosis immediately after acute bilateral carotid clamping, but that the blood flow rate was insufficient to maintain adequate oxygen delivery.

Regulation of steroid hydroxylase gene expression in the ovine fetal adrenal gland at 0.4 gestation

This study was designed to test the hypothesis that ACTH from the fetal pituitary is a major regulator of adrenocortical steroid hydroxylase gene expression in the ovine fetus at 0.4 (60-70 days) of gestation. Pregnant ewes at 0.4 gestation received intravenous infusions of dexamethasone (0.76 mg/h, n = 13) for 48 h. The rationale for this regime was that some of the infused dexamethasone would cross the placenta and act on the fetal pituitary to suppress ACTH release. Control animals received infusions of saline (0.38 ml/h, n = 12) for 48 h. At the end of the infusion period, the animals were killed, umbilical vessel blood taken for ACTH and cortisol analyses, and the fetal adrenal glands taken for assessment of P-450scc, P-450(17 alpha) and P-450c21 levels using the techniques of hybridization histochemistry and RNase protection assay. Dexamethasone treatment decreased maternal and fetal concentrations of ACTH to 29 +/- 10 and < 20 pg/ml, respectively and cortisol concentrations to 3.5 +/- 0.6 and 3.2 +/- 0.8 nmol/l respectively. The adrenal glands from the dexamethasone-treated fetuses exhibited significantly lower levels of mRNA for P-450scc (11% of control) and P-450(17 alpha) (2% of control). These results suggest that ACTH is a major regulator of steroid hydroxylase gene expression and subsequent cortisol biosynthesis in vivo in the ovine fetus at 0.4 gestation.

BLOOD VOLUME MEASUREMENTS IN THE NEONATAL LAMB: VALIDATION OF A METHOD USING [51Cr]-LABELLED RED CELLS

1. The reproducibility of blood volume measurements, using [51Cr]‐labelled red blood cells (RBC) was tested in three lambs, 79–89 days of age, and the accuracy was tested in eight lambs, 83± 0.4 days of age, in which blood volume was measured simultaneously by [51Cr]‐RBC and [125I]‐gamma globulin plus haematocrit (hct).

Fluid abnormalities occur in the chronically cannulated mid-gestation but not late gestation ovine fetus

Hydrops fetalis, with or without oligo- or polyhydramnios, is associated with very high fetal mortality. In many cases the causes are unknown. Chronically cannulated ovine fetuses have been used as animal models to study the regulation of fetal fluid balance. This study reports that the mid-gestation ovine fetus (70 ± 1 d of gestation; term = 145-150 d) is susceptible to the development of fetal abnormalities (excess allantoic fluid-hydrallantois, with or without hydrops and hydranencephaly), when blood vessels in the neck are cannulated. Cannulation of one carotid artery and one jugular vein, or cannulation of a single jugular vein resulted in 5 out of 12 fetuses having abnormalities 1 wk later. In contrast, six fetuses at 115 d of gestation that had both carotids and one jugular vein ligated cranially and cannulated, developed hydranencephaly but no hydrops or hydrallantois. In the mid-gestation fetus hydrallantois [760 ± 140 mL (n = 5) versus 104 ± 23 mL (n = 7 controls), p < 0.001] occurred without alterations in the plasma concentrations of ACTH, cortisol, atrial natriuretic peptide, or aldosterone, as well as without anemia. Although the causes of the fluid abnormalities were not resolved, it is important to note the developmental differences in vulnerability.

EFFECT OF ARGININE VASOPRESSIN AND PARATHYROID HORMONE-RELATED PROTEIN ON RENAL FUNCTION IN THE OVINE FOETUS

1. The effects of intravenous infusions of arginine vasopressin (AVP), parathyroid hormone‐related protein (PTHrP) and AVP + PTHrP on renal function in intact ovine foetuses at 100–125 days of gestation were examined.