Cyclosporine, but not FK506, selectively induces renal and coronary artery smooth muscle contraction

Surgery. 1998 Apr;123(4):456-60.


Background: Cyclosporine immunosuppression for organ transplantation is associated with hypertension and nephrotoxicity. Because the effects of cyclosporine as an immunosuppressant are mediated by the effect of cyclosporine as a phosphatase inhibitor, and phosphatase inhibitors are potent vascular smooth muscle contractile agents, we hypothesized that cyclosporine might induce contraction of the renal artery vascular smooth muscle directly.

Methods: Strips of bovine renal, carotid, superior mesenteric, or coronary arteries were obtained fresh from an abattoir. The strips were equilibrated in a muscle bath, and the contractile responses to cyclosporine and FK506 were determined.

Results: Cyclosporine (50 to 5000 micrograms/ml), but not FK506, induced rapidly developing, sustained contractions of renal and coronary artery smooth muscle. The magnitude of the cyclosporine-induced contractions of carotid and superior mesenteric artery smooth muscles was significantly less. The magnitude of renal artery smooth muscle contractions induced by cyclosporine was enhanced in the presence of an intact endothelium.

Conclusions: Although these effects occurred in vitro to relatively high doses of cyclosporine, these data suggest that cyclosporine may selectively induce renal artery smooth muscle contraction through activation of the Ca(2+)-dependent phosphatase (calcineurin) in the smooth muscle, and these contractions may be enhanced by the release of endothelial-derived contracting factors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cattle
  • Coronary Vessels / drug effects
  • Coronary Vessels / physiology*
  • Coronary Vessels / ultrastructure
  • Cyclosporine / pharmacology*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology
  • Endothelium, Vascular / ultrastructure
  • In Vitro Techniques
  • Microscopy, Electron, Scanning
  • Muscle Contraction / drug effects*
  • Muscle Contraction / physiology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology*
  • Muscle, Smooth, Vascular / ultrastructure
  • Renal Artery / drug effects
  • Renal Artery / physiology*
  • Renal Artery / ultrastructure
  • Tacrolimus / pharmacology*
  • Time Factors


  • Cyclosporine
  • Tacrolimus