The selective adenosine A(1) receptor antagonist KW-3902 prevents radiocontrast media-induced nephropathy in rats with chronic nitric oxide deficiency

Several studies have recently suggested a principal role of adenosine in th e pathogenesis of radiocontrast media-induced nephropathy. In the present e xperiments, we therefore investigated the renal protective effects of 8-(no radamantan-3-yl)-1,3-dipropylxanthine (KW-3902), a potent and selective ade nosine A(1) receptor antagonist, on radiocontrast media-induced nephropathy in the model of the N-<(<omega>)over bar>-nitro-L-arginine methyl ester (L -NAME) hypertensive, chronic nitric oxide (NO)-depleted rat. Chronic NO dep letion was induced by pretreatment with L-NAME, 50 mg/ml, added to drinking water for 8 weeks. Clearance experiments were performed in anesthetized ra ts and glomerular filtration rate was assessed prior to and following the a pplication of high osmolar radiocontrast media (sodium diatrizoate, 3 ml/kg , i.v.) or an equivalent volume of isoosmolar mannitol to examine the role of hyperosmolarity in radiocontrast media-induced nephropathy. Subgroups re ceived KW-3902 (0.1 mg/kg, i.v.), 20 min prior to radiocontrast media admin istration. Age-matched, untreated rats served as controls. Radiocontrast me dia application induced a significant decline in glomerular filtration rate in L-NAME hypertensive animals, whereas no effects were observed in contro l rats. KW-3902 fully prevented the drop in glomeruIar filtration rate in r esponse to radiocontrast media in L-NAME hypertensive rats, No renal hemody namic alterations were observed in mannitol-infused animals. The present ex periments demonstrate that the decrease in glomerular filtration rate follo wing radiocontrast media occurred independently of the osmotic load, and th at KW-3902 effectively prevented the radiocontrast media-induced deteriorat ion in renal function. KW-3902 may be especially beneficial in patients at high risk for developing acute renal failure following radiocontrast media application or in patients in which extracellular fluid volume expansion is limited by clinical conditions such as congestive heart failure. (C) 2001 Elsevier Science B.V. All rights reserved.