[The significance of eicosanoids in glomerular diseases]

Prostanoids are local cyclooxygenase products, synthesized by mesangial and epithelial cells of the glomerulus as well as by a variety of inflammatory cells and platelets. Prostaglandins and thromboxane have direct vasodilatory and vasoconstrictory effects and can modulate glomerular function. Arachidonic acid, the main substrate for cyclooxygenase, can also be metabolized by the lipoxygenase pathway to leukotrienes, substances which are primarily synthesized in inflammatory cells. In several models induction of immunologic glomerular injury is associated with an increased glomerular formation of cyclooxygenase and lipoxygenase products. The changes in cyclooxygenase products have been shown to account for some hemodynamic changes found in some of these models. Increased renal prostanoid formation is also present in patients with glomerular disease. There is some evidence that increased renal PG-formation in patients with moderate glomerular disease regulates GFR and mediates proteinurie in some of these patients. Leukotrienes are chemotactive substances which modulate the function of inflammatory cells, stimulate the growth of mesangial cells, and constrict mesangial cells in culture. Thus, these compounds might be mediators in the induction of immune mediated glomerular disease.