title: Mitigation of experimental radiation nephropathy by renin-equivalent doses of angiotensin converting enzyme inhibitors.
abstract: OBJECTIVE
  We tested five different angiotensin converting enzyme inhibitors (ACEI) as mitigators of experimental radiation nephropathy at drug doses calibrated to the plasma renin activity (PRA). This was done to determine whether all ACEI had the same efficacy as mitigators of radiation nephropathy when used at drug doses that gave equivalent suppression of the renin angiotensin system.
  
  
  METHODS
  10 Gy total body irradiation with bone marrow transplantation was used to cause radiation nephropathy in barrier-maintained rats. Equivalent ACEI doses were determined based on their effect to inhibit angiotensin converting enzyme (ACE) and raise the PRA in unirradiated animals.
  
  
  RESULTS
  PRA-equivalent doses were found for captopril, lisinopril, enalapril, ramipril and fosinopril. These doses overlap the human doses of these drugs on a body surface area basis. All ACE inhibitors, except fosinopril, mitigated radiation nephropathy; captopril was a somewhat better mitigator than lisinopril, enalapril or ramipril.
  
  
  CONCLUSIONS
  Most, but not all, ACEI mitigate radiation nephropathy at doses that overlap their clinically-used doses (on a body surface area basis). Fosinopril is known to be an ineffective mitigator of radiation pneumonitis, and it also does not mitigate radiation nephropathy. These pre-clinical data are critical in planning human studies of the mitigation of normal tissue radiation injury.
authors.affiliation: Radiation Oncology, Medical College of Wisconsin , Milwaukee , Wisconsin.
authors.forename: John E
authors.initials: JE
authors.lastname: Moulder
authors.forename: Eric P
authors.initials: EP
authors.lastname: Cohen
authors.forename: Brian L
authors.initials: BL
authors.lastname: Fish
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002138:Calibration; D002216:Captopril / Q000008:administration & dosage; D004656:Enalapril / Q000008:administration & dosage; D017328:Fosinopril / Q000008:administration & dosage / Q000737:chemistry; D007668:Kidney / Q000528:radiation effects; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology; D017706:Lisinopril / Q000008:administration & dosage; D008297:Male; D011832:Radiation Injuries / Q000188:drug therapy* / Q000209:etiology; D017257:Ramipril / Q000008:administration & dosage; D051381:Rats; D012083:Renin / Q000097:blood / Q000737:chemistry*; D012084:Renin-Angiotensin System / Q000187:drug effects; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D004656:Enalapril; D002216:Captopril; D017706:Lisinopril; D012083:Renin; D017257:Ramipril; D017328:Fosinopril
keywords: ACE inhibitors; captopril; mitigation; plasma renin activity; radiation nephropathy; total body irradiation