The objective of the present proposal is elucidation of mechanism(s) responsible for decrements in both plasma osmolality and the osmotic threshold for AVP release during gestation.
Specific aims are: (1) Test the hypothesis that changes in osmoregulation during pregnancy are due a decrease in """"""""effective blood volume"""""""" or to other hemodynamic alterations which affect AVP secretion. (2) Using an in vitro hypothalamo-neurohypophysial explant determine a) whether AVP secretion is increased in pregnancy, b) if gestational osmoregulatory changes are due to a circulating factor and, c) whether AVP secretory alterations in pregnancy are dependent on afferent neural input to the hypothalamus and/or pituitary. Proposed experiments are: I. Determine renal, humoral, hemodynamic and osmoregulatory responses of gravid rats subjected to chronic volume expansion comparing them with animals ingesting a normal or sodium restricted diet. II. Examine osmoregulatory responses of gravid rats subjected to chronic vasoconstrictor treatment. III. Attempt to reproduce the osmoregulatory changes of pregnancy in virgin rats by mimicking gestational hemodynamic and hormonal alterations via production of arterio-venous fistula in combination with chronic estrogen therapy. IV. Determine basal and osmotically stimulated AVP secretion in vitro from hypothalamo-neurohypophysial tissue of gravid rats at various stages of gestations using organ explant and perifusion methodologies. The effects of incubating neural tissue in plasma from virgin and pregnant animals on AVP secretion will also be studied. Vasopressin has been implicated in several forms of hypertension. More importantly, volume homeostasis, water metabolism, AVP secretion and control of blood pressure in normal pregnancy remain poorly understood. Information gained from present investigations will contribute to a better understanding of these physiologic processes and may lead to improvements in the care of pregnant patients with high blood pressure and/or renal disease, disorders in which water handling and volume regulation are markedly abnormal.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Human Embryology and Development Subcommittee 2 (HED)
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University of Chicago
Schools of Medicine
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Hines, T; Lindheimer, M D; Barron, W M (1994) Effect of autonomic blockade on pressor responses to vasopressin in pregnant rats. Am J Obstet Gynecol 171:1296-302
Hines, T; Lindheimer, M D; Barron, W M (1993) Total autonomic blockade eliminates the attenuated pressor response to angiotensin II in pregnant rats. Am J Physiol 265:R1270-5
Hines, T; Barron, W M (1992) Effect of sinoaortic denervation on pressor responses in pregnant rats. Am J Physiol 262:R1100-5
Umans, J G; Lindheimer, M D; Barron, W M (1990) Pressor effect of endothelium-derived relaxing factor inhibition in conscious virgin and gravid rats. Am J Physiol 259:F293-6
Pan, Z R; Lindheimer, M D; Bailin, J et al. (1990) Regulation of blood pressure in pregnancy: pressor system blockade and stimulation. Am J Physiol 258:H1559-72
Barron, W M; Lindheimer, M D (1988) Osmoregulation in pseudopregnant and prolactin-treated rats: comparison with normal gestation. Am J Physiol 254:R478-84