ALTERED NAC1 TRANSPORT IN HENLE'S LOOP IN--MODELS OF HYPERTENSION

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This project will focus on identifying the intrarenal site or sites of altered sodium reabsorption in two well established models of experimental hypertension. Studies will utilize the method of perfusing isolated tubule segments of specific pathogen-free Sprague-Dawley rats, Dahl S and R rats, and Brattleboro rats with diabetes insipidus. Although these animal models have been extensively studied previously utilizing other research techniques, the application of the isolated tubule technique in the rat has been limited. This new development will allow direct correlation of results of in vitro perfusion with previous results from in vivo micropuncture of the same animal model of hypertension. Methodologies will involve measurement of net and unidirectional ion fluxes and transepithelial voltages in isolated, perfused segments of the loop of Henle in the hypertensive models. Studies will directly evaluate the effect of renal denervation on sodium chloride transport in the DOCA-salt model, will examine the effect of Dahl S plasma on salt transport in both normal and Dahl distal nephron segments, and will examine the sites of action by which DOCA and vasopressin effect salt transport in the Brattleboro rat. These studies should provide information concerning the site or sites in the distal nephron that may contribute to altered sodium transport in these experimental models of hypertension.