LAZAROIDS PREVENT ACUTE CYCLOSPORINE-INDUCED RENAL VASOCONSTRICTION

Citation
Rj. Krysztopik et al., LAZAROIDS PREVENT ACUTE CYCLOSPORINE-INDUCED RENAL VASOCONSTRICTION, Transplantation, 63(9), 1997, pp. 1215-1220
Citations number
42
Categorie Soggetti
Immunology,Surgery,Transplantation
Journal title
ISSN journal
00411337
Volume
63
Issue
9
Year of publication
1997
Pages
1215 - 1220
Database
ISI
SICI code
0041-1337(1997)63:9<1215:LPACRV>2.0.ZU;2-N
Abstract
Background. Cyclosporine (CsA)-induced nephrotoxicity may be due to in trarenal vasoconstriction and glomerular hypoperfusion. Several factor s, including endothelin and prostanoids, are suggested mediators of th is response. Recent evidence suggests that CsA leads to increased oxyg en-derived free radical (ODFR) production and lipid peroxidation in re nal tissue. Whether this leads to alterations in renal vessel reactivi ty is unclear. Lazaroids, such as U74389G, are radical-quenching antio xidants that inhibit ODFR-induced lipid peroxidation and may improve r enal function after ischemia and reperfusion. We hypothesized that ODF Rs contribute to CsA-induced alterations of the renal microcirculation . Methods. Rat hydronephrotic kidneys were studied by video microscopy . Interlobular arteriolar diameter and flow, afferent and efferent art eriolar diameters, and cardiac output were measured at 15-min interval s for 120 min. U74389G or its vehicle was infused 15 min before topica l application of CsA to the kidney. The results were compared with U74 389G alone and normal saline. Results. CsA administration caused renal microvascular vasoconstriction (10-25% below baseline) and hypoperfus ion (35% below baseline). Both vasoconstriction and hypoperfusion were significantly attenuated by U74389G (5-8% and 20% below baseline, res pectively). Conclusions. Inhibition of lipid peroxidation by U74389G m aintained renal blood flow during acute CsA administration. These data suggest that ODFRs are involved in the renal microvascular response t o CsA. Inhibition of ODFR-induced lipid peroxidation may help prevent CsA-induced glomerular hypoperfusion. Lazaroids may prove an effective adjunct in reducing CsA-induced nephrotoxicity.