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Sympathetic nervous system hyperactivity has been postulated to play a major role in the intense intrarenal vasospasm and hypertension provoked by cyclosporine. It has been argued that the denervated renal allograft may be partially protected from the tubulointerstitial fibrosis associated with chronic cyclosporine administration compared with innervated kidneys in extrarenal transplantation.Utilizing a model of chronic cyclosporine nephropathy in which striped fibrosis develops in the uninephrectomized salt-depleted rat, the effect of renal denervation on renal structure and function was examined. Sprague-Dawley rats maintained on a low-salt diet underwent uninephrectomy and contralateral renal denervation or sham denervation, followed by cyclosporine 15 mg/kg daily by injection.After 21 days, glomerular filtration was markedly depressed and linear zones of tubular atrophy and interstitial fibrosis had developed compared with vehicle-treated control animals (P <0.001). However, there was no significant difference in either renal function or structure between denervated and sham-operated animals treated with cyclosporine.We conclude that renal sympathetic neural hyperactivity is not important in the development of chronic cyclosporine nephropathy.