STIMULATION OF THE CIRCULATING RENIN-ANGIOTENSIN SYSTEM BY CHRONIC HYPOGLYCAEMIA IN LATE GESTATION FETAL SHEEP
Amanda C. Boyce, Karen J. Gibson, Eugenie R. Lumbers, Department of Physiology & Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052.
We examined effects of a sustained reduction in maternal and fetal arterial glucose concentrations on fetal growth, the fetal kidney and renin-angiotensin system in chronically catheterised pregnant sheep. In 9 ewes (121 days gestation, term≈150 days), maternal glucose concentrations were lowered and maintained between 1.7 and 1.9 mmol L−1 for 12-13 days by i.v. infusion of insulin (27.0 ± 2.0 mU kg−1 h−1). Seven control ewes received vehicle (20% maternal plasma in 0.15M saline, 0.0378 mL kg−1 h−1).
During insulin infusion, maternal arterial glucose concentrations were 40% lower than in control animals (P<0.001). Fetal glucose levels were 31% lower (P<0.001). Fetal arterial Po2 increased during hypoglycaemia; average daily values were 23.5 ± 0.6 mmHg compared with 19.4 ± 0.6 mmHg in normoglycaemic fetuses (P<0.001). Pco2 was lower than in the normoglycaemic group throughout (P<0.05) and arterial pH was higher (P<0.05). Plasma potassium levels increased (from 3.8 ± 0.2 to 4.5 ± 0.2 mmol L−1; P< 0.005) and correlated negatively with fetal glucose levels (r2=0.73, P<0.05, n=8). Apart from consequent increases in potassium excretion, renal function (urine flow rate, urine osmolality, GFR, renal excretion and reabsorption rates) was largely unaffected.
Fetal body and kidney weight were not different to normoglycaemic values. However, longitudinal growth rates were 28% lower during hypoglycaemia, and kidney weights in hypoglycaemic fetuses were directly related to longitudinal growth (r2=0.86, P<0.005, n=8). Renal renin levels, and renal mRNA levels for renin, angiotensinogen and angiotensin receptor subtypes 1 and 2 were similar in each group, but during hypoglycaemia circulating renin levels increased from control levels of 2.1 ± 0.6 to 7.6 ± 2.8 ng angiotensin I mL−1 h−1 (P=0.01). Thus an increase in circulating renin-angiotensin system activity, like that observed at delivery in hypoxaemic growth-restricted infants1,2, was induced in an animal model of undernutrition, in the absence of hypoxaemia.
(1) Kingdom JC, McQueen J, Connell JM, Whittle MJ. British Journal of Obstetrics and Gynaecology. 1993;100:476-482.
(2) Konje JC, Bell SC, Morton JJ, de Chazal R, Taylor DJ. Clinical Science. 1996;91:169-175.
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