The overall objective of this proposal is to study, during normal and pathological conditions, the role of the sympathetic system in modulating renal hemodynamics and renal function during development using chronically catheterized and conscious fetal, newborn and adult sheep. I) The first major objective of this proposal will be to test the hypothesis that the renal hemodynamic and functional responses to Alpha, Beta, and dopamine receptor stimulation differ between fetal, newborn and adult animals. More specifically, this proposal is designed to investigate the ability of renal Alpha, Beta, and dopaminergic receptors to (a) modulate renal vascular tone, and (b) glomerular filtration rate, sodium and water metabolism, and renin release during development. Intrarenal infusion of different Alpha, Beta and dopamine agonists and antagonists will be used. Moreover, (c) results from these in vivo experiments will be correlated to in vitro characterization of renal Alpha, Beta and dopaminergic receptors in fetal, newborn and adult sheep. II) The second major objective of this proposal is to determine the role of circulating catecholamines and sympathetic nervous system in the fetal renal response to hypoxemia. We are speculating that there is a hierarchy in the mechanisms controlling renal hemodynamics and function during fetal hypoxemia, renal nerve activation modulating acute changes and circulating catecholamines modulating long-term effects of hypoxemia. Moreover, we are suggesting that these mechanisms may have different developmental patterns. More specifically, we are proposing to study in young (less than 115 days gestation) and near-term (greater than 135 days gestation; term 145 days) fetal lambs (a) the role of renal nerves, and (b) the contribution of circulating catecholamines in modulating the renal hemodynamic and functional responses to severe (pO2 about 8 mmHg) and moderate (pO2 about 14 mmHg) hypoxemia. Moreover, (c) the role of renal prostaglandins in attenuating the effects of sympathetically mediated renal vasoconstriction during severe and moderate hypoxemia will be studied. In summary, understanding of the fetal and neonatal renal responsiveness to sympathetic stimulation a) may have immediate clinical relevance since adrenergic agents are presently used in neonatal intensive care situations, and b) is essential for the development of new concepts regarding intrauterine therapy and management of the fetus during high-risk pregnancies and of severely sick premature infants.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD020576-01
Application #
3318800
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1985-09-30
Project End
1990-08-31
Budget Start
1985-09-30
Budget End
1986-08-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Robillard, J E; Segar, J L; Smith, F G et al. (1992) Regulation of sodium metabolism and extracellular fluid volume during development. Clin Perinatol 19:15-31
Robillard, J E; Smith, F G; Segar, J L et al. (1992) Mechanisms regulating renal sodium excretion during development. Pediatr Nephrol 6:205-13
Smith, F G; Klinkefus, J M; Robillard, J E (1992) Effects of volume expansion on renal sympathetic nerve activity and cardiovascular and renal function in lambs. Am J Physiol 262:R651-8
Page, W V; Perlman, S; Smith, F G et al. (1992) Renal nerves modulate kidney renin gene expression during the transition from fetal to newborn life. Am J Physiol 262:R459-63
Smith, F G; Smith, B A; Segar, J L et al. (1991) Endocrine effects of ventilation, oxygenation and cord occlusion in near-term fetal sheep. J Dev Physiol 15:133-8
Smith, F G; Smith, B A; Guillery, E N et al. (1991) Role of renal sympathetic nerves in lambs during the transition from fetal to newborn life. J Clin Invest 88:1988-94
Olson, A L; Robillard, J E; Kisker, C T et al. (1991) Negative regulation of angiotensinogen gene expression by glucocorticoids in fetal sheep liver. Pediatr Res 30:256-60
Smith, F G; Sato, T; McWeeny, O J et al. (1990) Role of renal sympathetic nerves in response of the ovine fetus to volume expansion. Am J Physiol 259:R1050-5
Robillard, J E; Smith, F G; Nakamura, K T et al. (1990) Neural control of renal hemodynamics and function during development. Pediatr Nephrol 4:436-41
Olson, A L; Perlman, S; Robillard, J E (1990) Developmental regulation of angiotensinogen gene expression in sheep. Pediatr Res 28:183-5

Showing the most recent 10 out of 31 publications