[Changing of renal endothelium-dependent vascular reactivity by cyclosporin A]

Clinical use of the immunosuppressant cyclosporine A (CSA) is hampered by its nephrotoxicity. The renal vascular resistance is increased, may be as a consequence of a deleterious effect of the drug on the vascular endothelial cell function. The renal effects of a subchronic treatment with CSA (50 mg/kg/d, sc, 18 days), or olive oil vehicule (1 ml/kg), were studied in normotensive male Wistar rats. Creatinine clearance was measured on 24 h urine collection before the right kidney of the animals was isolated and perfused in an open circuit at 6 ml/min with Tyrode's solution. Renal vasodilator responses to acetylcholine (ACH, 10(-10) to 10(-7) M) and sodium nitroprusside (NP, 3 x 10(-9) to 3 x 10(-6) M) were studied after reestablishment of a renal vascular tone by a continuous perfusion of noradrenaline (NA, 10(-7) M). ACH was more potent than NP to induce renal vasodilation (EC50 = 0.57 +/- 0.05 x 10(-9) M, n = 8, vs 3.42 +/- 0.29 x 10(-8) M, n = 5), but both drugs reversed the NA-induced vasoconstriction by near 90%. L-NAME (3 x 10(-5) M) had no effect on NP-induced renal relaxation but suppressed responses to low concentrations of ACH and decreased by half its Emax (47 +/- 17%).(ABSTRACT TRUNCATED AT 250 WORDS)