SYMPATHETIC CONTROL OF RENAL FUNCTION DURING DEVELOPMENT

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This proposal is designed to determine the functional roles of catecholamines and the sympathetic nervous system in modulating renal hemodynamics and function during development in conscious and chronically catheterized fetal, newborn and adult sheep. Moreover, these physiological findings will be correlated to in vitro determination of alpha, beta and dopaminergic receptors in the developing kidney. Specific aims are to study: 1) the ability of renal alpha, beta and dopaminergic receptors to modulate renal vascular tone during development; and 2) the ability of alpha, beta and dopaminergic receptors to modulate glomerular filtration rate, sodium and water metabolism and renin secretion during development. Intrarenal alpha, beta and dopaminergic agonists and antagonists will be administered. Changes in renal blood flow will be determined by a pulsed doppler flow probe. These experiments will reveal important information concerning the mechanisms modulating the renal vascular and renal functional response to sympathetic stimulation during development in fetal, newborn and adult sheep. Moreover, for the first time these studies will permit correlation of the physiologic characteristics of the renal sympathetic system with the in vitro characterization of renal adrenoceptors (alpha, beta and DA) in the same animal during development from fetal to adult life. The information obtained from these experiments will have significant clinical implications since alpha and beta adrenoceptor agonists and antagonists, as well as dopamine, are presently used in neonatal intensive care situations. The sensitivity of the renal vasculature to these agents, however, is not currently known in premature infants. Dr. Nakamura, the candidate, has completed his clinical training in neonatology, and has been supported for the past two years (Jan 1983 to Dec 1984) by a National Research Service Award (F32-HD-06438) to do laboratory research in the field of developmental physiology. His research training background as well as his research productivity during that period of time are evidence of the candidate's serious intent to enter into a successful academic research career. Dr. Robillard, the sponsor, is a foremost developmental physiologist with specific expertise in fetal renal function. His research techniques and investigative skills using the unanesthetized and chronic fetal lamb model will provide the candidate with unique skills necessary to pursue independent research.