Thromboxane renal production

NAF nafimidone. nafagrel [inn] (DP 1904) is an imidazolylmethylnaphthalenecarboxylic acid, a THROMBOXANE SYNTHETASE INHIBITOR. It inhibits renal thromboxane B2 production and renal damage in hypertensive diabetic rats, nafamostat [inn] (nafamostat mesylate [usan] nafamostat mesilate [jan] FUT 175) is a naphthyl derivative, an ENZYME INHIBITOR active as a (serine) PROTEASE inhibitor and anticomplement agent. It acts as an ANTIFIBRINOLYTIC and PLATELET AGGREGATION INHIBITOR, and can be used for the treatment of acute pancreatitis and cerebrovascular disorders. 

Patrono, C., Ciabattoni, G., Remuzzi, G., Gotti, E., Bombardieri, S., DiMunno, -O., Tartarelli, G., Cinotti, G.A., Simonetti, B.M. and Pierucci, A. (1985). Functional significance of renal prostacyclin and thromboxane A2 production in patients with systemic lupus erythematosus. ]. Clin. Invest., 76, 1011-1018... 

The renal production of thromboxanes seems to be very low normally. In certain conditions, however, the capacity of the kidney for thromboxane biosynthesis increases greatly. Thus, ureteral obstruction led to the appearance of TXA 2 as well as of large amounts of PGEj in the venous effluent of the affected kidney [346,347]. This biosynthesis was demonstrated both in the cortex and the medulla. The interplay between the enhanced production of the va.sodilatory PGEj and the vasoconstrictive TXA 2 was believed to be of importance for regulating the in vivo renal perfusion pressure in the hydronephrotic kidney. 

The roles of leukotrienes and cytochrome P450 products in the human kidney are currently speculative. Recently, the 5,6-epoxide has been shown to be a powerful vasodilator in animal experiments. Another recent discovery is that free radicals attack arachidonic acid-containing phospholipids to yield an 8-ep/-PGF2[J that has powerful thromboxane-like properties. Synthesis is not blocked by COX inhibitors but can be blocked by antioxidants. This vasoconstrictor, which is present in humans, is thought to be another important mediator causing renal failure in the hepatorenal syndrome. 

Coffman TM, Carr DR, Yarger WE, Klotman PE. Evidence that renal prostaglandin and thromboxane production is stimulated in chronic cyclosporine nephrotoxicity.Transplantation 1987 43 282-285. 

Changes in the pattern of prostanoid production during obstructive uropathy affect renal function primarily through alterations in renal haemodynamics. In general, enhanced biosynthesis of vasodilatory prostanoids occurs with acute obstruction, while increases in thromboxane synthesis prevail in the later stages. The role of eicosanoids in obstruction will be discussed in detail below. 

Kelley, V.E., Sneve, S. and Musinski, S. (1986). Increased renal thromboxane production in murine lupus nephritis. ]. Clin. Invest., 77, 252-259... 

Coffman, T.M., Yarger, W.E. and Klotman, P.E. (1985). Functional role of thromboxane production by acutely rejecting renal allografts in rats. /. Clin. Invest., 75, 1242-1248... 

Benabe, J.E., Klahr, S., HofifiTian, M.K. and Morrison, A.R. (1980). Production of thromboxane by the kidney in glycerol-induced acute renal failure in the rabbit. Prostaglandin, 19, 333-347... 

Altboum, I., Boswell, J. and Kelley, V.E. (1986). Thromboxane production by activated renal cortical macrophages. Presented at the American Society of Nephrology, December 7-10, Washington D.C. 

Thromboxane is synthesized by the kidney [52] and the production is enhanced in many situations leading to renal failure, i.e. uretereal obstruction (in the rabbit [53], in the rat [54]), renal vein constriction [55] and glycerol induced renal failure [56]. TXAj is the major metabolite of arachidonic acid in human cortical hydronephrotic tissue [57]. 

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