AN EXPERIMENTAL-STUDY OF ALTERED NITRIC-OXIDE METABOLISM AS A MECHANISM OF CYCLOSPORINE-INDUCED RENAL VASOCONSTRICTION

Nephrotoxicity caused by cyclosporin A (CSA) is the result of vasocons triction of the renal microcirculation. The endothelium-derived relaxi ng factor nitric oxide (NO) regulates microvascular blood flow in vari ous tissues, and mediates the microcirculatory response during hyperte nsion and sepsis. This study investigated the role of NO in CSA-induce d renal vasoconstriction. Hydronephrotic kidneys in rats were suspende d in an environmentally controlled tissue bath, and interlobular, affe rent and efferent arteriolar diameters and blood flow were measured by in vivo videomicroscopy. CSA was administered alone, with the nitric oxide synthase (NOS) inhibitor N-omega-nitro-L-arginine methyl ester ( L-NAME) or with exogenous NOS substrate L-arginine. CSA significantly constricted the whole of the renal microvasculature whereas L-NAME alo ne preferentially constricted the preglomerular vessels. L-Arginine re versed the vasoconstriction induced by CSA whereas L-NAME had no furth er effect. Preglomerular basal vascular tone is dependent on continuou s production of NO and alterations in the L-arginine-NO pathway contri bute to CSA-induced renal vasoconstriction.