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1 Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Torrance, CA, USA
* To whom correspondence should be addressed. E-mail: mikeross{at}ucla.edu.
Objective: Maternal water restriction acutely increases maternal and fetal plasma sodium and osmolality and may subsequently induce long-term physiological changes in the offspring. The accompanying dehydration (Dehy)-induced anorexia also may effect fetal growth and development via nutrient reduction. We determined the impact of prenatal hypertonicity (Pre-Dehy) on offspring cardiovascular and osmoregulatory function in 1 month old lambs. Methods: Pre-Dehy singleton lambs (n=6) were exposed to in utero hypernatremia (8-10 mEq increase; 110 to 150 days of gestation) induced by maternal water restriction. A matched group of Control singleton lambs (n=6) were born to ewes provided ad libitum water and food throughout gestation. After delivery, all ewes were provided ad libitum water, and all newborns allowed ad libitum nursing. At 15±2 d of age, lambs were prepared with vascular and bladder catheters and studied at 21±2 d. Following a 2-hour basal period, lambs received an IV infusion of hypotonic (0.075M) NaCl (0.15 ml/kg/h) for an additional 2 hours. Lamb arterial blood pressure was continuously monitored and arterial blood samples obtained prior to, during and following the infusion. Results: During the basal period, Pre-Dehy lambs had significantly increased plasma osmolality (302±1 and 294±1 mOsm/kg, p<0.01) and sodium levels (144±1 vs 140±1 mEq/L; p<0.01), hematocrit (28±1 vs 25±1 %, p<0.05), and systolic (96±2 vs 87±2 mmHg, p<0.001), diastolic (66±2 vs 53±1 mmHg, p<0.001) and mean arterial pressures (79±2 vs 68±1 mmHg, p<0.001) than Controls. Despite the infusion of hypotonic saline, Pre-Dehy lambs continued to exhibit relative hypertonicity (304±2 mOsm/kg), hypernatremia (145±1 mEq/L) and hypertension (mean blood pressure, 80±2 mmHg) as compared to Controls. However plasma arginine vasopressin, glomerular filtration rate (GFR), and urinary osmolar and sodium excretion and clearance (per kg body weight) were similar in both groups of neonates. Conclusions: Offspring of prenatally water restricted ewes exhibit hypernatremia, hypertonicity and hypertension, which persists despite hypotonic saline infusion. In utero hypertonicity and perhaps maternal nutrient stress may program offspring osmoregulation and systemic arterial hypertension.
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