Recent work from this and other laboratories strongly implicate the distal nephron as a major site for the regulation of Ca and PO4 excretion. Despite considerable insights already obtained regarding physiologic control of Ca & PO4 transport, pathophysioloic states resulting in altered rates of excretion remain largely unexplored. Several models will be examined by in vivo micropuncture of the rat nephron to evaluate the tubular mechanisms involved in: 1. Renal PO4 retention in Spontaneous Hypertensive Rats 2. Renal PO4 wastage in rats with Spontaneous Hypercalciuria 3. The Hypercalciuria a). in Spontaneous Hypercalciuric rats, & b). during DOCA escape, as well as 4. The hypocalciuric response to a). a low Ca diet b). vitamin D analogues). amiloride & similar diuretics Together, these studies attempt to test the hypothesis that internephron heterogeneity with regard to Ca & PO4 transport is an """"""""induced"""""""" phenomenon, elicited by pharmacologic manipulations, which is otherwise """"""""dormant"""""""" in most physiologic settings. Tubular fluid will be obtained from superficial and in appropriate models accessible papillary structures and determined for Ca, Na, & PO4 by the electron probe as previously published (1,3). The chronic parathyroidectomized rats will be used to optimize the conditions for detecting abnormalities in PO4 handling by the hypertensive and the hypercalciuric rats. The acute PTK preparation will be used to study Ca transport to avoid marked falls in filtered loads of Ca with chronic PTK. Data from these models will advance the current concepts regarding disturbances of renal Ca & PO4 metabolism in patients with essential hypertension, idiopathic hypercalciuria, Conn's syndrome, and vitamin D deficiency, and in patients ingesting a low Ca diet or being treated with """"""""hypocalciuric diuretics. Evaluation of the interplay between ghe superficial and the juxtamedullary nephrons under a wide spectrum of pathophysiologic states will help define the relative roles of these nephron segments in the final regulation of Ca and PO4 excretion.
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