Modulation of body fluids and angiotensin II receptors in a rat model of intra-uterine growth restriction.

We previously reported that sodium restriction during pregnancy reduces plasma volume expansion and promotes intra-uterine growth restriction (IUGR) in rats while it activates the renin-angiotensin-aldosterone system (RAAS). In the present study, we proceeded to determine whether expression of the two angiotensin II (ANGII) receptor subtypes (AT(1) and AT(2)) change in relation to maternal water-electrolyte homeostasis and fetal growth. To this end, pregnant (gestation day 15) and non-pregnant Sprague-Dawley rats were randomly assigned to two groups fed either normal, or Na(+)-restricted diets for 7 days. At the end of the treatment period, plasma aldosterone and renin activity as well as plasma and urine electrolytes were measured. Determinations for AT(1) and AT(2) mRNA and protein were made by RNase protection assay and photoaffinity labelling, respectively, using a number of tissues implicated in volume regulation and fetal growth. In non-pregnant rats, Na(+) restriction decreases Na(+) excretion without altering plasma volume, plasma Na(+) concentration or the expression of AT(1) and AT(2) mRNA or protein in the tissues examined. In normally fed pregnant rats when compared to non-pregnant controls, AT(1) mRNA increases in the hypothalamus as well as pituitary and declines in uterine arteries, while AT(1) protein decreases in the kidney and AT(2) mRNA declines in the adrenal cortex. In pregnant rats, Na(+) restriction induces a decrease in plasma Na(+), an increase in plasma urea, as well as a decline in renal urea and creatinine clearance rates. Protein levels for both AT(1) and AT(2) in the pituitary and AT(2) mRNA in the adrenal cortex are lower in the Na(+)-restricted pregnant group when compared to normally fed pregnant animals. Na(+) restriction also induces a decrease in AT(1) protein in the placenta. In conclusion, these results suggest that pregnancy may increase sensitivity to Na(+) depletion by the tissue-specific modulation of ANGII receptors. Finally, these receptors may be implicated in the IUGR response to low Na(+).