title: Heparin decreases blood pressure and response to exogenous endothelin but does not protect against chronic experimental cyclosporine nephropathy.
abstract: Cyclosporine nephrotoxicity is caused by renal arteriolar vasoconstriction 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 endogenous endothelin 1 production. In a model of chronic cyclosporine nephrotoxicity 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 marked decrease in responsivity to exogenous endothelin. Despite this, there were no beneficial effects on renal structure or function in this animal model of chronic cyclosporine nephrotoxicity. Thus, the role of endothelin in the pathogenesis of the chronic tubulointerstitial changes and arteriolopathy in this model is probably minor.
authors.affiliation: Division of Nephrology, Hypertension, and Clinical Pharmacology Oregon Health Sciences University Portland 97201, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: Bennett
authors.forename: N
authors.initials: N
authors.lastname: Franceschini
authors.forename: C
authors.initials: C
authors.lastname: Alpers
authors.forename: J
authors.initials: J
authors.lastname: Lindsley
authors.forename: T F
authors.initials: TF
authors.lastname: Andoh
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects*; D016572:Cyclosporine / Q000633:toxicity*; D019332:Endothelin-1 / Q000494:pharmacology*; D005355:Fibrosis; D006493:Heparin / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008297:Male; D009395:Nephritis, Interstitial / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019332:Endothelin-1; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D006493:Heparin