The structural and functional interrelationships between the macula densa, extraglomerular mesangium, and other cells of the juxtaglomerular apparatus (JGA) are incompletely understood. In addition, few studies on the development of this area of the nephron have been undertaken. We intend to use a combination of physiological, morphological, and immunocytochemical techniques to describe, at a cellular level, the structure and function of the JGA in vivo and in vitro. First, using the isolated thick ascending limb with attached glomerulus, we will examine in vitro and in tissue fixed for electron microscopy structural rearrangements within intra- and extracellular compartments that might occur during changes in luminal osmolality. Second, the permeability properties of the extracellular matrix of the JGA will be tested in vitro with the addition of sized fluorphores and tracers for light and electron microscopy added to the bathing solution. Third, we intend to label in vivo the extracellular matrix of the developing JGA of newborn rats and rabbits to study its sequence of assembly and cellular origin. In addition, the appearance of renin- and angiotensin-containing cells will be determined immunocytochemically and correlated with the stage of glomerular development. Fourth, the acquisition of functional properties of the JGA will be determined by measuring plasma renin levels in developing animals and renin release from the isolated thick ascending limb with attached JGA preparation. Ultimately, these experiments in normal animals will be extended to genetic and experimental models of hypertension to determine whether JGA dysfunction and/or abnormal JGA development might be one of the relevant factors contributing to the development of hypertension.
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