The juxtaglomerular apparatus links the glomerulus, where plasma undergoes filtration to form primary urine, and a late nephron site at which tubular fluid is markedly reduced in volume and concentration by tubular absorption. By detecting changes in fluid composition the tubular cells at the contact point, the macula densa cells, are able to receive and transmit a message that affects the rate of filtration in the glomerulus. Increases in NaCl concentration depress filtration rate. Thus, the juxtaglomerular apparatus serves to stabilize the concentration of NaCl entering the distal portions of the nephron by negative feedback coupling. The precise relation between the tubular signal and filtration rate (and therefore the regulatory potential of this feedback system) is variable with tight coupling in states of dehydration and loose coupling in states of extracellular volume expansion. A special cell population within the juxtaglomerular apparatus, the granular cells, is the site of synthesis of renin, the proteolytic enzyme involved in the generation of angiotensin II. Release of renin is controlled in part by distal tubule fluid composition using the macula densa-granule cell pathway. Thus, the macula densa serves two functions in the control of body fluid volumes, regulation of distal nephron NaCl delivery and control of plasma angiotensin concentration, a hormone with multiple effects on Na balance. Experiments will be carried out to develop a better understanding of the mechanisms causing the change in the relationship between the macula densa signal and filtration rate and its functional consequences and to define the relation between the dual role of the macula densa as a controller of filtration rate on the one hand and of renin release on the other. Studies will use a combination of micropuncture and isolated perfused tubule methods for study of single nephron function, and will utilize a recently developed ultra-micro renin assay method that permits accurate measurement of single nephron renin release. The following general propositions will be tested experimentally: 1) the macula densa mediated changes in filtration rate and renin secretion are initiated by identical cellular responses to a luminal signal. 2) the sensitivity of the macula densa mechanism for filtration rate control is affected by the net balance of vasodilator and vasoconstrictor influences prevailing at a given time and does not reflect a primary alteration in intrinsic function of the juxtaglomerular apparatus.
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