The overall objective of this proposal is to determine the developmental changes in the arterial baroreflex during fetal and postnatal life in sheep and to investigate the mechanisms controlling these changes. The first objective will be to test the hypothesis that the increased activity of the renin-angiotensin system during fetal and neonatal life contributes to the developmental changes in the baroreflex control of heart rate and efferent sympathetic nerve activity. The second objective will be to test the hypothesis that endogenous prostaglandins contribute to the increased sensitivity of the baroreflex control of renal sympathetic nerve activity early during development. The third objective of this application will be to test the hypothesis that circulating vasopressin facilitates the baroreflex-mediated reduction in peripheral sympathetic nerve activity in fetal and newborn animals. These studies should give new and important information on the functional development of the arterial baroreflex and of the mechanisms controlling these changes. Adequate understanding of these phenomena is of particular significance during fetal and neonatal life since any maturational alterations in the autonomic nervous system may acutely influence organ flow, affect fetal and postnatal organ growth and development, lead to predisposition of developing hypertension later in life, and have been suggested as a potential cause of the sudden infant death syndrome.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL002865-03
Application #
2210697
Study Section
Special Emphasis Panel (ZHL1-CCT-L (01))
Project Start
1993-03-01
Project End
1998-02-28
Budget Start
1995-03-01
Budget End
1996-02-29
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Iowa
Department
Pediatrics
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Samyn, M E; Petershack, J A; Bedell, K A et al. (1998) Ontogeny and regulation of cardiac angiotensin types 1 and 2 receptors during fetal life in sheep. Pediatr Res 44:323-9
Segar, J L; Scholz, T D; Bedell, K A et al. (1997) Angiotensin AT1 receptor blockade fails to attenuate pressure-overload cardiac hypertrophy in fetal sheep. Am J Physiol 273:R1501-8
Segar, J L; Minnick, A; Nuyt, A M et al. (1997) Role of endogenous ANG II and AT1 receptors in regulating arterial baroreflex responses in newborn lambs. Am J Physiol 272:R1862-73
Segar, J L (1997) Ontogeny of the arterial and cardiopulmonary baroreflex during fetal and postnatal life. Am J Physiol 273:R457-71