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Fetal Physiological Programming

Prenatal programming of hypernatremia and hypertension in neonatal lambs

Department of Obstetrics and Gynecology, University of California, Los Angeles, Harbor-UCLA Medical Center, Torrance, California

Submitted 13 May 2004 ; accepted in final form 2 September 2004

Maternal water restriction and the accompanying dehydration-induced anorexia may induce long-term physiological changes in offspring. We determined the impact of prenatal hypertonicity (Pre-Dehy) on offspring cardiovascular and osmoregulatory function. Pre-Dehy lambs were exposed to in utero hypernatremia (8- to 10-meq increase; 110–150 days of gestation) induced by maternal water restriction. Control lambs were born to ewes provided ad libitum water and food throughout gestation. After delivery, all ewes were provided ad libitum water and all newborns were allowed ad libitum nursing. Lambs were prepared with vascular and bladder catheters at 15 ± 2 days of age and studied at 21 ± 2 days. After a 2-h basal period, lambs received an infusion of hypotonic (0.075 M) NaCl (0.15 ml·kg^–1·h^–1 iv) for 2 h. Lamb arterial blood pressure was monitored, and blood samples were obtained before, during, and after infusion. During the neonatal basal period, Pre-Dehy lambs had significantly increased plasma osmolality (302 ± 1 vs. 294 ± 1 mosmol/kgH₂O, P < 0.01), sodium levels (144 ± 1 vs. 140 ± 1 meq/l, P < 0.01), hematocrit (28 ± 1% vs. 25 ± 1%, P < 0.05), and mean arterial blood pressure (79 ± 2 vs. 68 ± 1 mmHg, P < 0.001) compared with control lambs. Despite the infusion of hypotonic saline, Pre-Dehy lambs maintained relative hypertonicity, hypernatremia, and hypertension. However, plasma arginine vasopressin, glomerular filtration rate, and urinary osmolar and sodium excretion and clearance (per kg body wt) were similar in the groups. Offspring of prenatally water-restricted ewes exhibit hypernatremia, hypertonicity, and hypertension, which persist despite hypotonic saline infusion. In utero hypertonicity and perhaps maternal nutrient stress may program offspring osmoregulation and systemic arterial hypertension.

sheep; osmolality; vasopressin

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