The overall objective of this proposal is to study the role of renal sympathetic innervation in regulating renal hemodynamics and function during renal maturation using chronically-instrumented fetal, newborn and 6 week old sheep. I. The first major objective will be to test the hypothesis that the renal sympathetic response to volume expansion (VE) changes during development. To test this hypothesis, we are proposing a) to study the effects of VE on renal sympathetic nerve activity (RSNA), renal hemodynamics and function during fetal and postnatal life and to determine if these effects are developmentally regulated; b) to examine the effect of renal maturation on the relationship between physiological changes in RSNA during VE and simultaneous changes in renal norepinephrine (NE) spillover and renal function; and c) to investigate the ontogeny and the role of sinoaortic and cardiopulmonary reflexes in modulating the changes in RSNA and renal function observed during VE in fetal and newborn sheep. II. The second major objective will be to test the hypothesis that the renal sympathetic system and circulating catecholamines play different roles in regulating the renal hemodynamic and functional responses to hemorrhage in fetal, newborn and 6 week old sheep, and that the effects of these systems on the immature kidney are developmentally regulated. To test this hypothesis, we are proposing a) to investigate the effects of nonhypotensive and hypotensive hemorrhage on RSNA, renal hemodynamics and function, and to determine if these effects are developmentally regulated; b) to correlate changes in RSNA with changes in renal NE spillover and renin release; c) to determine the role of cardiopulmonary and sinoaortic baroreflexes in regulating the changes in RSNA, renal function and renin production in response to hemorrhage during development; d) to evaluate the effect of renal denervation on renal function, and renin production in response to hemorrhage during renal ontogeny; and to determine the role of circulating catecholamines in modulating these responses. III. The third major objective will be a) to test the hypothesis that renal nerves play an important role in regulating renin gene expression and intrarenal distribution of renin mRNA during development and b) to determine the role of cardiopulmonary receptors in modulating renin gene expression during the transition from fetal to newborn life. These studies should give new and important information on the functional development of the renal sympathetic innervation and of its influences on the control of renal function and volume regulation during fetal and postnatal life.
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