Endothelin mediates the renal vasoconstriction induced by cyclosporine in the rat

J Am Soc Nephrol. 1990 Jul;1(1):76-83.


The effect of cyclosporine on renal function was first investigated in the isolated perfused rat kidney. Kidneys from normal male Sprague-Dawley rats were perfused at constant pressure. After control clearance periods, cyclosporine (0.6, 1.2, or 3 mg/min) or vehicle was infused over 5 min period in the renal artery and then four 10-min experimental periods followed. Cyclosporine, but not vehicle caused a dose dependent fall in renal perfusate flow associated with a concomitant increase in renal vascular resistance. Glomerular filtration rate was also decreased in parallel. We also examined whether endogenous endothelin mediates cyclosporine-induced acute renal vasoconstriction. In isolated kidneys pre-exposed to specific anti-endothelin antibody and then challenged with cyclosporine (1.2 mg/min) the renal perfusate flow, renal resistance, and glomerular filtration rate were 22.3 +/- 1.8 ml/min, 4.50 +/- 0.36 mmHg/ml.min-1, 1.06 +/- 0.05 ml/min, respectively, as compared with 12.9 +/- 1.2 ml/min, 7.8 +/- 1.2 mmHg/ml.min-1, 0.55 +/- 0.06 ml/min (P less than 0.01) measured in isolated kidneys pre-exposed to a non-immunized rabbit serum. The effectiveness and specificity of anti-endothelin antibody were confirmed by its capability of preventing the renal function deterioration caused by a single bolus dose (150 pmol) of synthetic endothelin, but not by infusion of angiotensin II, norepinephrine, or thromboxane A2 mimetic U-46619 in isolated kidneys. To test further the relationship between endogenous endothelin and cyclosporine-induced renal vasoconstriction, a second series of in vivo studies was performed in normal rats.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / physiopathology
  • Animals
  • Antibodies / administration & dosage
  • Cyclosporins / toxicity*
  • Endothelins / antagonists & inhibitors
  • Endothelins / physiology*
  • In Vitro Techniques
  • Male
  • Perfusion
  • Rats
  • Rats, Inbred Strains
  • Renal Circulation / drug effects*
  • Renal Circulation / physiology
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology


  • Antibodies
  • Cyclosporins
  • Endothelins