The glomerular physiology of lipoxin-A.

Abstract

A number of renal diseases, such as acute and chronic glomerulonephritis, acute interstitial nephritis, allograft rejection, and others are characterized by the presence inflammatory cellular infiltrates consisting, at various stages, of neutrophils, macrophages, monocytes, eosinophils, and lymphocytes. In addition, these disease processes are often accompanied by impairment of glomerular perfusion, filtration, and permselectivity functions. Despite much controversy as to the mediator systems involved in the initiation and perpetuation of these glomerular functional abnormalities, consensus has emerged as to the central role of leukocyte-derived biologically active cytokines1. In this regard, lipid-derived mediators, including platelet activating factor and the cyclooxygenase and lipoxygenase (LO) products of arachidonate metabolism have received particular attention. An understanding of the role played by these locally released compounds in the pathophysiology of glomerular injury can only result from a close integration of the best available bioanalytic and physiologic technologies, and the application of both approaches to experimental disease models, in conjunction with selective antagonism of specific mediators through receptor antagonists and enzyme inhibitors. Using glomerular micropuncture techniques, we have identified the responses of the glomerular microcirculation to peptidyl leukotrienes2,3 and, utilizing selective antagonists, proposed a role for these compounds in mediating the reductions in renal plasma flow and glomerular filtration, as well as the induction of proteinuria, in endotoxin- and anti-glomerular basement membrane antibody-induced glomerular injury4,5. In more recent studies6, we have examined the effects of exogenously administered lipoxin A (LX-A) on the glomerular microcirculation in the rat. Our results indicate that, in sharp contrast to sulfidopeptide LTs, the predominant action of LX-A is to increase renal perfusion. This response appears to be evoked by selective reduction in preglomerular resistance with a consequent augmentation of single nephron and whole kidney glomerular filtration rate.KeywordsLeft Renal ArteryAcute Interstitial NephritisColloid Osmotic PressureArteriolar ResistanceSingle Nephron Glomerular Filtration RateThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.