PHYSIOLOGY-ADRENERGIC INFLUENCE ON RENAL FLUID TRANSFER

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Although an important regulatory role of the adrenergic nervous system in renal function has been suspected for many years, it is only in the past several years that the functional significance of this system has been fully demonstrated experimentally in the regulation of salt and fluid transfer at the glomerular and tubular levels. In this proposal of 5-year research projects, the PI will focus on elucidating the physiological mechanisms which underlie the somewhat puzzling phenomena for solute and fluid patterns observed in animal models of acute ECF volume depletion and congestive heart failure. Whereas these two conditions are characterized by a seemingly similar systemic milieu, particularly, enhanced adrenergic nerve activity, proximal salt and water reabsorption appear to be enhanced only in animals with congestive heart failure. In the proposed projects, the PI intends to characterize the details of proximal tubule transport system in these two cnditions and seek to ascertain the role of the adrenergic nerves in this transport system. Furthermore, attempts will be made to test the hypothetical possibility that the chronicity of activation of the adrenergic system accounts for the observed transport patterns by affecting the underlying mechanisms. Since proximal tubule reabsorption of salt and water involves both transepithelial and transcapillary transfer of substances, the experimental approach includes studies of both of these processes.