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Submitted on February 12, 2003
Accepted on July 1, 2003
1 Perinatal Research Laboratories, David Geffen School of Medicine at University of California Los Angeles, Department of Obstetrics and Gynecology, Harbor-University of California Los Angeles Medical Center, Torrance, California 90502, USA
* To whom correspondence should be addressed. E-mail: mdesai{at}obgyn.humc.edu.
Lambs exposed in utero to maternal hypertonicity demonstrate plasma hypertonicity and arterial hypertension. To determine whether hypertonicity is due to an altered osmoregulatory setpoint, we examined arginine-vasopressin (AVP) and cardiovascular responses to hypertonic saline infusion in these offspring.
Study lambs (Dehy) were exposed to maternal hypernatremia (8-10 mEq/liter increase; 110d to 150d of gestation) induced by water-restriction. Control singleton and control twins were born to ewes provided ad libitum water. We anticipated reduced birth weight due to maternal dehydration-induced anorexia and therefore included a control group of twin gestations, to approach a similar birth weight near term. After delivery, ewes from all three groups were provided ad libitum water and their newborns allowed ad libitum nursing. At 15 ± 2d of age, lambs were prepared with bladder and vascular catheters. At 23 ± 2d, after a 2 h basal period, neonatal lambs were intravenously infused with hypertonic 0.83M NaCl (0.075 ml/kg/h) for 2 h followed by a 2 h recovery. Neonatal mean arterial pressure (MAP), urine flow were continuously monitored and blood samples obtained before, during and following infusion.
During the basal period, Dehy neonates and Control twins demonstrated significantly increased plasma sodium levels and MAP than Control singletons. In addition, the Dehy neonates had significantly increased plasma osmolality compared with Control singletons and twins. In response to hypertonic infusion, the Dehy offspring continued to exhibit hypertonicity and hypertension. Importantly, plasma tonicity and blood pressure were greatest in Dehy singletons, lowest in singleton controls and intermediate in twin controls. Further, the plasma osmolality threshold for AVP secretion was significantly higher in Dehy singletons (290 ± 2 mOsm/kg) than Controls twin (285 ± 1 mOsm/kg) and Control singletons (280 ± 2 mOsm/kg), indicating in utero programing of an altered setpoint for systemic osmolality and blood pressure regulation. As both twin gestation and dehydration-anorexia incur potential fetal nutritional stress, the results suggest that both in utero hypertonicity and nutrition reduction contribute to offspring programing. We postulate that the nutritional stress associated with twins (as well as dehydration induced anorexia) contributes to increased plasma sodium levels, while the increased plasma osmolality is due to in utero hypertonicity.
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