title: An experimental study of altered nitric oxide metabolism as a mechanism of cyclosporin-induced renal vasoconstriction.
abstract: Nephrotoxicity caused by cyclosporin A (CSA) is the result of vasoconstriction of the renal microcirculation. The endothelium-derived relaxing factor nitric oxide (NO) regulates microvascular blood flow in various tissues, and mediates the microcirculatory response during hypertension and sepsis. This study investigated the role of NO in CSA-induced renal vasoconstriction. Hydronephrotic kidneys in rats were suspended in an environmentally controlled tissue bath, and interlobular, afferent 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 alone preferentially constricted the preglomerular vessels. L-Arginine reversed the vasoconstriction induced by CSA whereas L-NAME had no further effect. Preglomerular basal vascular tone is dependent on continuous production of NO and alterations in the L-arginine-NO pathway contribute to CSA-induced renal vasoconstriction.
authors.affiliation: Department of Surgery, University of Louisville School of Medicine, Kentucky, USA.
authors.forename: I T
authors.initials: IT
authors.lastname: Bloom
authors.forename: F R
authors.initials: FR
authors.lastname: Bentley
authors.forename: D A
authors.initials: DA
authors.lastname: Spain
authors.forename: R N
authors.initials: RN
authors.lastname: Garrison
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D016572:Cyclosporine / Q000009:adverse effects / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply; D008297:Male; D008833:Microcirculation; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D009569:Nitric Oxide; D016572:Cyclosporine