The purpose of the present studies is to investigate the potential role of non-cyclooxygenase-derived arachidonic acid (AA) metabolites to modulate renal hemodynamics and sodium metabolism in vivo. Recent studies from several laboratories have confirmed the existence of several novel non-prostanoid, AA metabolites in the mammalian kidney; a finding of great potential importance in view of the known renal effects of certain prostanoid AA metabolites in the kidney: e.g. a major role in maintaining renal perfusion under conditions of impaired cardiac output states and extracellular fluid volume depletion has been demonstrated for these compounds in humans. Furthermore, the capacity of the kidney to elaborate prostnoid metabolites of AA is altered in certain renal diseases possibly as a manifestation of adaptation to the altered microenvironment of a pathophysiologic state. The novel pathway metabolites of AA thus far isolated in the kidney have not been shown to produce biologic effects in vivo or in vitro. The project herein proposes to systematically evaluate the biologic activity of selected classes of novel metabolites in whole animals utilizing classical renal clearance techniques. The studies will employ direct renal infusions of exogenous synthetic metabolites known to be produced by the kidney from previous in vitro metabolic studies. In addition procedures for isolation and identification of specific novel compounds in the urine and renal venous plasma will be developed during the course of these studies. Finally the interaction of novel AA metabolites with the reninangiotensin system as it relates to autoregulation of renal blood flow and glomerular filtration rate in the whole kidney will be investigated.
| Preisig, P A; Toto, R D; Alpern, R J (1987) Carbonic anhydrase inhibitors. Ren Physiol 10:136-59 |
