Faculty Collaboration Database

Angiotensin II receptor antagonists in the treatment and prevention of radiation nephropathy. Int J Radiat Biol 1998 Apr;73(4):415-21

Date

05/20/1998

Pubmed ID

9587080

DOI

10.1080/095530098142257

Scopus ID

2-s2.0-0031944621 (requires institutional sign-in at Scopus site)   46 Citations

Abstract

PURPOSE: Angiotensin-converting enzyme (ACE) inhibitors are effective in the prophylaxis of radiation-induced renal and lung injury. Studies were designed to determine whether blocking the angiotensin II (AII) receptor, rather than blocking AII synthesis with ACE inhibitors, would also be effective.

MATERIALS AND METHODS: Rats received total body irradiation (TBI) followed by bone marrow transplantation (BMT), and were randomized to: an ACE inhibitor (captopril); an AII type 1 (AT1) receptor antagonist (L-158,809); or no treatment. Drug therapy began 9 days prior to BMT and continued for the duration of the study.

RESULTS: Analysis of renal function, histopathology and animal survival showed that the AII blocker was more effective than the ACE inhibitor in the prophylaxis of BMT nephropathy. Further studies have shown that the AII blocker is as effective as captopril in the treatment of established radiation nephropathy, and that the AII blocker is at least as effective as captopril in the prophylaxis of lung injury induced by chemo-radiation therapy.

CONCLUSIONS: These studies indicate that blockage of the AT1 receptor by itself is sufficient for the treatment of radiation-induced renal and lung injury, hence the renin-angiotensin system is fundamentally involved in the pathogenesis of these injuries. These studies provide further evidence that there is more to late radiation injuries than delayed mitotic cell death.

Author List

Moulder JE, Fish BL, Cohen EP

MESH terms used to index this publication - Major topics in bold

Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Animals
Antihypertensive Agents
Bone Marrow Transplantation
Captopril
Imidazoles
Kidney
Lung
Radiation Injuries, Experimental
Radiation-Protective Agents
Rats
Renal Insufficiency
Renin-Angiotensin System
Tetrazoles