AB S T R A C T Osmoregulation was studied in near term and age-matched Sprague-Dawley rats. Basal plasma osmolality (Posm) and plasma sodium (PNa) were 281+3 mosmol/kg and 134+3 meq/liter, respectively, on the 20th gestational day compared with 292+±3 mosmol/kg and 140+1 meq/liter in virgin animals (P < 0.001), whereas Purea and plasma water content were similar in pregnant and control rats. These differences could not be reproduced in animals receiving progesterone, estrone, or a combination of progesterone and estradiol for 2 wk.Pregnant and control rats were deprived of water for changes (A%) were significantly greater in the gravid animals (P < 0.01). Therefore, Posm was increased without concomitant volume depletion by intraperitoneal hypertonic saline. Again PAVP VS. Posm correlated significantly (r > 0.9; P < 0.001) in each group, and the apparent threshold was 14 mosmol lower in pregnant animals. Diluting ability, tested by oral water loading, was not impaired in the pregnant animals which excreted a 30 ml/kg load as well as controls. Also, chronically hydrated virgin animals whose fluid intake was more than twice that of pregnant rats (for 19 d) did not lower their Posm.In separate studies homozygous Brattleboro rats, which produce no endogenous vasopressin, were also shown to have a decreased Posm (pregnant 292 +4 mosmol/kg; virgin 310+6 mosmol/kg P < 0.001), but unchanged Uosm during pregnancy.Data demonstrate a resetting ofthe osmostat in gravid Sprague-Dawley rats as Posm and the threshold for AVP secretion both decrease significantly during gestation in this species. Studies in homozygous Brattleboro animals with hereditary diabetes insipidus suggest that the osmotic threshold for thirst is reset as well. INTRODUCTION Plasma osmolality decreases during normal human pregnancy to values that range 5-10 mosmol/kg below that of nonpregnant women (1-3). This decrement is apparent by the 6th gestational wk and is sustained until term. If such a reduction in osmolality occurred in a nongravid subject she would cease secreting antidiuretic hormone (ADH)l and enter a state of con-

A s bstract. We previously observed that osmoregulation and the osmotic threshold for antidiuretic hormone secretion were altered during pregnancy in SpragueDawley rats and the present study evaluated the influence of volume on arginine vasopressin (AVP) release during gestation in this species. Basal plasma osmolality (Posm) and intravascular volume were 297±3 mosmol/kg and 16.2±1.2 ml in virgin animals compared with 290±2 mosmol/kg and 20.2±2.3 ml in 14-d pregnant rats and 287±3 mosmol/kg and 25.2±2.3 ml in 21-d (near-term) pregnant rats (P < 0.001, each pregnant group vs. virgin). Isosmotic volume depletion was produced by intraperitoneal polyethylene glycol. Volume decreased from 1 to 26% and blood pressure remained stable during decrements as high as 16%. Plasma AVP (PAvp) did not rise significantly in either group ofpregnant animals or virgin controls until blood volume depletion reached 6-7%, after which levels rose in a similar exponential manner in virgin, 14-d, and 21 -d pregnant animals. In terms of absolute changes, however, PAvp in gravid rats started to increase when intravascular volume was still considerably greater than basal blood volume in the nonpregnant controls.Other experiments, where Posm was increased by intraperitoneal hypertonic saline, reconfirmed that the osmotic threshold for AVP secretion was reduced 10 mosmol/kg during pregnancy and that AVP release was stimulated by increments in body tonicity as small as 1-2%. In parallel studies, blood volume contraction and increases in Posm were evoked by intraperitoneal polyethylene glycol dissolved in hypertonic saline and results compared with animals receiving intraperitoneal saline alone. Decrements in volume (n7%), which alone would increase PAvp minimally, increased the sensitivity of the secretory response to changes in osmolality two-to threefold, an effect which was similar in virgin and gravid animals. Finally, restricting water intake of pregnant rats to that of virgins on days 16-20 of gestation led to suboptimal volume expansion, hypertonicity, and an exaggerated increase in PAVP.These results demonstrate that despite an intravascular space which at term is nearly twice that of virgin rats, pregnant animals secrete AVP in response to fractional volume depletion in a manner similar to nonpregnant controls; that is, the relationship between total blood volume and AVP secretion is altered during gestation such that the expanded blood volume is recognized as normal.

No abstract

Osmoregulation during pregnancy was compared in Brattleboro rats completely lacking vasopressin [homozygous (DI)], those with partial deficiency [heterozygous (HZ)], and control Long-Evans (LE) animals. Plasma osmolality (Posmol) was decreased 10-16 mosmol/kg near term in each group, whereas urine osmolality (Uosmol) was similar to that of virgin controls. This was accompanied by significant increments in water turnover similar in HZ and LE and massive in the gravid DI. Chronic vasopressin treatment increased Uosmol less in pregnant DI compared with virgins (P less than 0.001), and urinary prostaglandin E2 was increased in all gravid groups. Captopril per os failed to implicate the renin-angiotensin system in the altered water ingestive behavior of pregnancy. Basal arginine vasopressin pressure (PAVP) was similar in gravid and virgin HZ and LE, whereas the osmotic threshold for AVP secretion was lower in both pregnant groups. Increasing Posmol by dehydration or hypertonic saline led to similar increments in plasma AVP (PAVP) in pregnant and nongravid rats of each group, but sensitivity of the system delta P AVP/delta P osmol was significantly lower in HZ, a difference compatible with the decreased pituitary AVP content in the HZ strain. Data are consistent with decreases in the osmotic thresholds for AVP release (in HZ and LE) and thirst (in DI) and a need for increased AVP secretion during pregnancy.

No abstract