Cyclosporine A nephrotoxicity in Goldblatt renovascular hypertension in rats

Experiments were conducted on a renovascular model of hypertension to investigate the effect of high blood pressure and CyA nephrotoxicity combined on arteriolar and tubular morphology and renal function. A two kidney, one clip model of Goldblatt hypertension was selected in which were given 20 or 40 mg/kg/d CyA by gastric gavage for 3-4 weeks while receiving isotonic saline as drinking fluid. CyA was found to suppress feeding and drinking and, as a result, lead to volume depletion and weight loss, with a corresponding lowering of blood pressure and renal function and an increase in plasma renin. When CyA and control animals were pair-fed these effects disappeared, except for a modest depression of renal function, unaccompanied by a reduction in urinary concentrating power. Histological damage to the tubules was equally prevalent in both kidneys despite different levels of renal perfusion, suggesting that plasma concentration, rather than toxin delivery, determines tubular damage. The occurrence of arteriolopathy and glomerulosclerosis was infrequent, and if present, it was only found in the unclipped kidney and was not potentiated by CyA. Glomerular prostaglandin synthesis after substrate incubation was suppressed by CyA to an equal extent in both kidneys, clipped and unclipped.