RENAL MICROVASCULAR FUNCTION IN AGED RATS

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This NIA Pilot Research Grant application (RO3) application is focused on directly examining renal microvascular function in the kidneys of aging animals for the purpose of establishing critical data on primary microvascular function and to obtain the essential preliminary data for preparation of a more comprehensive RO1 proposal in the coming year. Currently, no studies have directly examined renal microvascular function in aged animals yet reduced renal function is commonly associated with the age-related decline in physiologic cardiovascular homeostasis. Experiments will be performed in vitro using the blood perfused juxtamedullary nephron technique. This unique preparation provides direct accessibility to afferent and efferent arterioles of the rat kidney in a blood perfused setting. Importantly, this is accomplished while preserving the anatomical relationships between the tubules and vasculature and allowing direct study of renal microcirculatory regulation under well-controlled conditions. This technique is highly sophisticated and has already made major contributions to defining what is known about renal hemodynamic control and renal microvascular function. By applying this unique approach we will address three basic specific aims. Aim 1 will determine the effect of aging on myogenic and tubuloglomerular feedback mediated autoregulatory efficiency in male and female rats. Aim 2 will directly assess segmental renal microvascular responsiveness to the renal vasoconstrictors, endothelin and angiotensin II. Aim 3 will directly assess the renal microvascular responsiveness to endothelium-dependent and endothelium-independent renal vasodilators, acetylcholine and nitric oxide. The data obtained will provide an accurate view of the behavior of afferent and efferent arterioles in young and aged, male and female rats. They will also provide the first direct functional evidence of the efficiency of renal autoregulatory behavior as well as the fundamental responsiveness to critically important renal vasoconstrictors and vasodilators. Application of these approaches to the study of microvascular function in kidneys of aged animals promises to provide unique insight into the impact of aging on microvascular function and renal microcirculatory regulation.