This proposal continues the original aims of HD5572, (to study the kidney and volume regulation in pregnancy focusing on water handling and antidiuretic hormone metabolism during normal and abnormal gestation. Objectives during the 11-15 yr period are: A) to elucidate factors responsible for the hypotonicity and decreased thresholds for drinking and vasopressin (AVP) secretion during pregnancy in the rat. Experiments will be performed in pseudopregnant animals to determine if the changes in osmoregulation described during rodent pregnancy requires the fetus and/or placentae. In other studies roles of angiotensin, endorphins and prolactin will be probed by either simulating the humoral milieu of gestation in virgin rats or inhibiting specific hormones (e.g.-angiotensin II with captopril; endorphins with naloxone) in gravid animals. B) Comparison of metabolic and renal clearances of AVP in gravid and virgin dogs, a species whose blood does not contain detectable vasopressinase during gestation and in non-human primates (cynanoglus monkeys) whose placentae produce this enzyme. These experiments will involve clearances of infused synthetic hormones and tracers, taking advantage of 1) our success in instantaneously inactivating vasopressinase when blood sampling and 2) use of a synthetic Tyr2-diodo-Arg8 vasopressin to produce a biologically active tritiated compound which will have a higher specific activity. This(3H)AVP (as well as iodinated tracer which is completely degraded by vasopressinase in vitro) will be infused intravenously into non-human primates to see is similar degradation occurs in vivo. C) Description of the osmotic thresholds for thirst and AVP secretion during normal human pregnancies and those complicated by hypertension. These studies evaluate the influence of water deprivation and loading, as well as the slow infusion of hypertonic saline (to normotensives only) on relationship between P(osm) and P(AVP) during gestation. Volume regulation in pregnancy is poorly understood and AVP could play a role in the oliguria and increased blood pressure during preeclampsia. Long term goals are to apply information obtained towards understanding water handling in pregnancy and managing abberations occurring in gestations complicated by hypertension.

R01HD005572

1978-05-01

1987-11-30