Prostaglandins and other arachidonic acid metabolites in the pathogenesis of clinical and experimental glomerulonephritis.

Isolated glomeruli, glomerular epithelial cells and mesangial cells contain the cyclooxygenase enzyme that converts arachidonic acid to prostaglandin (PG)-endoperoxides. Biologically active metabolites of the latter include PGE2, PGF2 alpha, PGI2 and Thromboxane (TX) A2. These substances modulate renal cortical functions, i.e. renin release, renal blood flow (RBF) and glomerular filtration rate. Acute glomerular injury (nephrotoxic serum nephritis) augments glomerular production of PGs and TXA2. Thromboxane A2 reduces glomerular function and inhibition of TXA2 synthesis preserves GFR and RBF in this disease model. Patients with chronic glomerulonephritis have a lower urinary excretion of 6-Keto-PGF1 alpha (the stable hydrolysis product of the vasodilator PGI2). In these patients, inhibition of PGI2 synthesis by a cyclooxygenase inhibitor leads to reductions in GFR and RBF inversely related to the basal urinary excretion of 6-Keto-PGF1 alpha. These findings suggest that in both acute and chronic glomerulonephritis, arachidonate metabolites may serve as pathophysiologic mediators of changes in glomerular function.