Renal and Platelet Eicosanoids in Chronic Glomerular Disease
Eicosanoid is the generic term which refers to lipoxygenase and cyclooxygenase products of arachidonate metabolism. Prostaglandins (PG) and the other eicosanoids are autacoids which do not have a circulating, endocrine function but rather act in a paracrine or autocrine manner affecting cells close to or at the site of PG synthesis1. Nonsteroidal anti-inflammatory drugs (NSAD) inhibit either irreversibly (aspirin) or reversibly the cyclooxygenase enzyme which converts arachidonate to the PG-endoperoxides. Presently, no similar inhibitory agents are clinically available which inhibit the lipoxygenase enzymes converting arachidonate to leukotrienes and monohydroxy fatty acids. Although glucocorticoids can limit substrate availability through the induction of a recently characterized phospholipase A2-inhibitory protein named lipocortin, their in vivo effects on endogenous PG production are rather inconsistent.
Unable to display preview. Download preview PDF.
- 1.M.J. Dunn, Renal prostaglandins, in: “Renal endocrinology”, M.J. Dunn ed., Williams and Wilkins, Baltimore (1983).Google Scholar
- 5.C. Patrono, G. Ciabattoni, G. Remuzzi, E. Gotti, S. Bombardieri, O. Di Munno, G. Tartarelli, G.A. Cinotti, B.M. Simonetti, and A. Pierucci, Functional significance of renal prostacyclin and thromboxane A2 production in patients with systemic lupus erythematosus. J. Clin. Invest. 76:1011 (1985).CrossRefGoogle Scholar
- 10.G. Ciabattoni, G.A. Cinotti, A. Pierucci, B. M. Simonetti, M. Manzi, F. Pugliese, P. Barsotti, G. Pecci, F. Taggi, and C. Patrono, Effects of sulindac and ibuprofen in patients with chronic glomerular disease. Evidence for the dependence of renal function on prostacyclin, N. Engl. J. Med. 310:279(1984).CrossRefGoogle Scholar
- 18.J.S. Cameron, Platelets in glomerular disease, Ann. Rev. Med.35:175 (1984).Google Scholar
- 21.A. Pierucci, B.M. Simonetti, G. Pecci, G. Mavrikakis, S. Feriozzi, G.A. Cinotti, P. Patrignani, G. Ciabattoni, and C. Patrono,Thromboxane antagonism improves renal function in lupus nephritis, N. Engl. J. Med. (in press).Google Scholar
- 26.M.L. Purkerson, J.H. Joist, J. Yates, and S. Klahr, Role of hypertension and coagulation in the progressive glomerulopathy of rats with subtotal renal ablation, Mineral Electrolyte Metab. 13: 370 (1987).Google Scholar
- 27.C. Zoja, A. Benigni, M. Livio, A. Bergamelli, S. Orisio, M. Abbate, T. Bertani, and G. Remuzzi, Selective inhibition of platelet thromboxane generation with low-dose aspirin does not protect rats with reduced renal mass from the development of progressive disease, Submitted for publication.Google Scholar
- 28.A. Brandis, G. Bianchi, E. Reale, U. Helmechen, and K. Kunn, Age-dependent glomerulosclerosis and proteinuria occurring in rats of the Milan normotensive strain and not in rats of the Milan hypertensive strain, J. Lab. Invest. 55:234 (1986).Google Scholar
- 29.F. Pugliese, P. Menè, and G.A. Cinotti, Glomerular prostaglandin and thromboxane synthesis in normotensive and hypertensive rats of the Milan strain before and after development of hypertension, J. Hypertension 4(suppl 3):S391 (1984).Google Scholar
- 30.P. Salvati, C. Ferti, L. Duzzi, R. Ferrario, N. Perico, G. Remuzzi, and G. Bianchi, Effect of thromboxane synthase inhibitor on age-dependent glomerulosclerosis in Milan normotensive rats [Abstract], 10th International Congress of Nephrology, London (1987).Google Scholar
- 31.P. Salvati, F. Pugliese, C. Ferti, L. Pierucci, R. Ferrario, and C. Patrono, Selective inhibition of glomerular thromboxane-synthase in rat models of progressive glomerulosclerosis, [Abstract], Kidney Int. (in press).Google Scholar
- 32.P. Patrignani, P. Filabozzi, F. Catella, F. Pugliese, and C. Patrono, Differential effects of dazoxiben, a selective thromboxane-synthase inhibitor, on platelet and renal prostaglandin endoperoxide metabolism, J. Pharmacol. Exp. Ther. 228:472 (1984).Google Scholar