Salt and Water Transporter Expression in Aging Kidneys

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With aging there is a progressive loss of renal concentrating ability. Acute illness in geriatric patients is often complicated by derangements in fluid and electrolyte balance that are costly, inconvenient and often delay recovery and prolong hospitalization. The long-term goal of this proposal is to better understand the process of salt and water balance in the intact aging kidney. Four water channels (aquaporins; AQP-1 to 4), four urea transporter isoforms (UT-A1 to 4), and several major sodium transporter proteins have been characterized in the nephron and vasa recta that are critical for renal regulation of salt and water balance and the urinary concentrating process. It is generally accepted that a decrease in the abundance of the vasopressin regulated water channel, AQP-2, contributes to diuresis seen with aging. The central hypotheses to be tested in these studies is that a decreased reabsorption of sodium, urea and water, independent of vasopressin and AQP-2 abundance, also contribute to this water loss. Our rationale is that an examination of the expression levels, intracellular distribution and regulation of these proteins with age will provide additional molecular understanding of the physiology and pathophysiology of this condition and lead to improvements in health care of the aged. To test this hypothesis we propose the following 2 Specific Aims: 1) Determine the abundance and intracellular distribution of proximal tubule and descending thin limb aquaporins-1, collecting dust aquaporins-2, -3 and -4, the four known medullary UT-A area isoforms and the major sodium channels among the nephron in young (3 month), middle aged (12 months) and elderly (24 months) F344XBNFI rats, a National Institute of Aging (NIA) endorsed model for renal aging studies. 2) Correlate plasma levels of vasopressin (ADH) and aldosterone with differences in transporter and channel protein abundance and intracellular in young, middle-aged and elderly F344xBNF1 (F344BN) rats. These studies are important because they will identify target transporters and hormonal relationships for future in-depth mechanistic investigations of this major disorder of the aged.