Since the introduction of cyclosporine in 1980, the 1-year survival rate after cardiac transplantation is now in excess of 80%.1 Despite the success experienced with cyclosporine, considerable morbidity remains associated with its use. Renal insufficiency characterized by renal vasoconstriction occurs frequently and limits the use of the drug.2 Hypertension occurs in >90% of cyclosporine-treated cardiac transplant recipients.3. In vitro cyclosporine damages endothelial cells, resulting in cell lysis and detachment.4 Endothelin represents a newly recognized polypeptide produced by vascular endothelium. Exogenous administration of endothelin results in intense renal and systemic vasoconstriction.5 Recently, investigators speculated that endothelin may mediate cyclosporine-induced hypertension and renal insufficiency.6. Recent studies in the rat7 using superpharmacologic doses of cyclosporine demonstrate cyclosporine-induced activation of plasma endothelin with an associated increase in renal vascular resistance. Administration of endothelin antisera reversed the renal vasoconstriction. The effect of clinically relevant doses of cyclosporine on the activation of circulating endothelin in humans has not been evaluated. The current study was designed to (1) investigate whether plasma endothelin is activated in cyclosporine- and non-cyclosporine-treated patients after cardiac transplantation, and (2) to determine if a correlation exists between plasma endothelin and systemic arterial pressure or serum creatinine after transplantation.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine