REGULATION OF RENAL CYCLOOXYGENASE-2

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The purpose of the application is to determine the mechanisms by which angiotensin II (AII) and endogenous glucocorticoids regulate expression of cyclooxygenase-2 in the kidney. The investigators propose that the following cascade occurs in medullary thick ascending limb of Henle's loop (mTAL): AII induces tumor necrosis factor-alpha (TNF) which in turn induces COX-2 gene expression which results in the production of PGE2. Sodium reabsorption in the mTAL is inhibited by PGE2 thus resulting in natriuresis. The specific aims of the project are 1) to determine the mechanism(s) by which AII increases COX-2 expression in the mTAL and other nephron segments, and 2) to assess the regulation of renal COX-2 by endogenous corticosteroids and phenotype of TAL and characterize cells that contain COX-2. These specific aims are an extension of the specific aims of the parent grant. The U.S. investigator will use cellular and molecular protocols while the foreign investigator will use in vivo models, immunohistochemical and in situ hybridization techniques to investigate the specific aims.