title: Protection against cyclosporine-induced impairment of renal microcirculation by verapamil in mice.
abstract: Fluorescence microscopy was used to examine the effect of cyclosporine (CsA) infusion on renal subcapsular (cortical) blood flow in 53 living mice, using FITC-dextran (MW: 156,000) as a fluorescent marker. CsA (8-19 mg/kg body weight) given i.v. for 1 min induced complete inhibition of blood flow. A complete standstill of flow was also obtained during a continuous infusion with a rate of 0.8-2 mg/kg/min. With lower infusion rates (0.15-0.23 mg/kg/min), blood flow was partially impaired. In all experiments, the decrease in flow occurred after a 15-25 min delay, suggesting a CsA metabolite or exhaustion of a protective mechanism as the causative agent. Pretreatment with an alpha-blocking agent, phentolamine (1.0 mg/kg), did not prevent the CsA-induced inhibition of blood flow. In contrast, pretreatment with a calcium antagonist, verapamil (0.3-0.4 mg/kg), prevented the impairment of blood flow at low (0.15-0.23 mg/kg/min), and partially at higher (0.8-2.4 mg/kg/min) rates of CsA infusion. Clinical studies are warranted to explore the role of calcium antagonists in the prevention of posttransplant acute cyclosporine-induced nephrotoxicity.
authors.affiliation: Department of Surgery, University of Texas Health Science Center, Dallas 75235.
authors.forename: P
authors.initials: P
authors.lastname: Rooth
authors.forename: I
authors.initials: I
authors.lastname: Dawidson
authors.forename: K
authors.initials: K
authors.lastname: Diller
authors.forename: I B
authors.initials: IB
authors.lastname: Täljedal
mesh_terms: D000818:Animals; D003524:Cyclosporins / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007262:Infusions, Intravenous; D007672:Kidney Cortex / Q000098:blood supply* / Q000187:drug effects; D051379:Mice; D008833:Microcirculation / Q000187:drug effects; D008856:Microscopy, Fluorescence; D010646:Phentolamine / Q000008:administration & dosage; D011292:Premedication; D014700:Verapamil / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D003524:Cyclosporins; D014700:Verapamil; D010646:Phentolamine