In fetal and adult mammals the neurohypophysial peptide arginine vasopressin (AVP) is secreted in response to similar osmotic and volume stimuli. In the fetus, AVP and arginine vasotocin (AVT) are physiologically important in the regulation of fetal lung fluid secretion and renal free water and sodium excretion. In adult mammals, the effects of the recently characterized atrial natriuretic peptide (ANP) on renal water and sodium excretion are, in general, opposite to the actions of AVP. However, the involvement of ANP in fetal renal function has not been investigated. The proposed studies have been designed to characterize the ontogenesis of AVP and/or AVT receptors, to define the secretion, metabolism and function(s) of ANP in the fetus and newborn, and to study the counter-regulatory actions of AVP and ANP on fetal water and salt metabolism and renal function. Initially, AVP and AVT actions in vivo will be differentiated on the basis of specific receptors (V1, V2 or AVT) by use of specific V1 and V2 receptor agonists and antagonists. In vitro studies will be performed to characterize the tissue distribution (renal, vascular, pulmonary and placenta) of AVP/AVT receptors and to quantify the ontogeny of receptor specificity and binding capacity, i.e., does fetal receptor maturation entail a transition from primarily AVT receptors to a population of AVP specific receptors. Subsequently, the ovine ANP will be isolated and in vivo studies of fetal, newborn and adult ANP secretion, metabolism and physiologic actions performed so that AVP and ANP physiologic effects may be compared. ANP receptor ontogeny also will be characterized in vitro. Finally, the counter-regulatory actions of AVP and ANP in terms of secretion and function will be investigated, both in vivo and in vitro. Chronically catheterized fetal, newborn and adult sheep will be the primary in vivo experimental models.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD006335-18
Application #
3310483
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1979-04-01
Project End
1993-03-31
Budget Start
1991-04-01
Budget End
1993-03-31
Support Year
18
Fiscal Year
1991
Total Cost
Indirect Cost
City
Torrance
State
CA
Country
United States
Zip Code
90502
Koos, B J; Mason, B A; Ervin, M G (1994) Adenosine mediates hypoxic release of arginine vasopressin in fetal sheep. Am J Physiol 266:R215-20
Ervin, M G; Terry, K A; Calvario, G C et al. (1994) Vascular effects alter early-gestation fetal renal responses to vasopressin. Am J Physiol 266:R722-9
Dodd, A; Kullama, L K; Ervin, M G et al. (1994) Ontogeny of ovine fetal renal atrial natriuretic factor receptors. Life Sci 54:1101-7
Ervin, M G; Terry, K A; Calvario, G C et al. (1993) Multiple receptor contributions to ovine fetal cardiovascular responses to vasopressin. Ann N Y Acad Sci 689:504-7
Ervin, M G; Kullama, L K; Ross, M G et al. (1993) Vasopressin receptors and effects during fetal development. Regul Pept 45:203-8
Fujino, Y; Ross, M G; Ervin, M G et al. (1992) Ovine maternal and fetal glomerular atrial natriuretic factor receptors: response to dehydration. Biol Neonate 62:120-6
Kullama, L K; Ross, M G; Lam, R et al. (1992) Ovine maternal and fetal renal vasopressin receptor response to maternal dehydration. Am J Obstet Gynecol 167:1717-22
Ervin, M G; Ross, M G; Leake, R D et al. (1992) V1- and V2-receptor contributions to ovine fetal renal and cardiovascular responses to vasopressin. Am J Physiol 262:R636-43
Ross, M G; Cardin, J P; Castro, L et al. (1991) Fetal and maternal plasma atrial natriuretic factor responses to angiotensin II infusion. Am J Obstet Gynecol 165:1635-41
Castro, R; Ervin, M G; Leake, R D et al. (1991) Effect of a ring-deleted atrial natriuretic factor analogue on ovine fetal renal and cardiovascular function. Pediatr Res 29:342-6

Showing the most recent 10 out of 47 publications