HEPARIN DECREASES BLOOD-PRESSURE AND RESPONSE TO EXOGENOUS ENDOTHELINBUT DOES NOT PROTECT AGAINST CHRONIC EXPERIMENTAL CYCLOSPORINE NEPHROPATHY

Cyclosporine nephrotoxicity is caused by renal arteriolar vasoconstric tion and tubulointerstitial fibrosis. Endothelin has been proposed as a major mediator of these phenomena. Heparin inhibits vascular smooth muscle cell proliferation and lowers blood pressure by regulating endo genous endothelin 1 production. In a model of chronic cyclosporine nep hrotoxicity in the rat, animals were treated with cyclosporine alone, cyclosporine plus heparin, and heparin alone for 28 days. Independent experiments determined that these doses of heparin resulted in a marke d decrease in responsivity to exogenous endothelin. Despite this, ther e were no beneficial effects on renal structure or function in this an imal model of chronic cyclosporine nephrotoxicity. Thus, the role of e ndothelin in the pathogenesis of the chronic tubulointerstitial change s and arteriolopathy in this model is probably minor.