Prostaglandins and other arachidonic acid metabolites in the kidney.

This very brief summary of the various possible contributions of PG to normal and abnormal renal function should highlight the problem of assigning a specific role to PG in overall renal physiology and pathophysiology. PG produced in specific segments of the nephron will affect specific functions occurring in this segment. These effects need not necessarily be reflected in the overall renal function. Also in some cases, the determinant may not be prostaglandins, that is, cyclooxygenase derivatives of AA, but perhaps lipoxygenase or epoxygenase products that influence the functional parameters of the specific segment. Despite the multitude of renal functions that may be influenced by PG, we would like to propose a teleological hypothesis for an overall role of PG in the kidney, that is, that of cytoprotective agents. Renal vasodilatatory prostaglandins will maintain renal blood flow when the latter is challenged, thus, preventing hypoxic injury to the tissue. Endogenous prostaglandins may also protect tubular cells from extreme environmental changes as may occur on both the luminal and contraluminal sides. For example, tubular cells may be exposed to luminal fluid that may vary from hypotonic to hypertonic, from alkaline to acid, and so forth. Similarly, the interstitial fluid osmolality and solute composition is subject to considerable variations which may be opposite to those existing on the urinary side. The role of PG might be to maintain the internal milieu of the cells exposed to such extreme changes in environment. This could be accomplished by changing the permeability characteristics of the membranes and the function of pumps. Thus, specific PGs could dampen the hormonal response to protect the specific nephron segment, which might otherwise suffer injury. This hypothesis might also help to explain why the effect of PG administration or inhibition of PG synthesis may vary considerably depending on the overall physiological state of the subject: Maintenance of a local internal milieu may require different responses from those required for total body homeostasis.