ANGIOTENSIN-II RECEPTOR ANTAGONISTS IN THE TREATMENT AND PREVENTION OF RADIATION NEPHROPATHY

Purpose: Angiotensin-converting enzyme (ACE) inhibitors are effective in the prophylaxis of radiation-induces renal and lung injury. Studies were designed to determine whether blocking the angiotensin II (AII) receptor, rather than blocking AII synthesis with ACE inhibitors, woul d also be effective. Materials and methods: Rats received total body i rradiation (TBI) followed by bone marrow transplantation (BMT), and we re randomized to: an ACE inhibitor (captopril); an AII type 1 (AT(1)) receptor antagonist (L-158,809); or no treatment. Drug therapy began 9 days prior to BMT and continued for the duration of the study. Result s: Analysis of renal function, histopathology and animal survival show ed that the AII blocker was more effective than the ACE inhibitor in t he prophylaxis of BMT nephropathy. Further studies have shown that the AII blocker is as effective as captopril in the treatment of establis hed radiation nephropathy, and that the AII blocker is at least as eff ective as captopril in the prophylaxis of lung injury induced by chemo -radiation therapy. Conclusions: These studies indicate that blockage of the AT(1) receptor by itself is sufficient for the treatment of rad iation-induced renal and lung injury, hence the renin-angiotensin syst em is fundamentally involved in the pathogenesis of these injuries. Th ese studies provide further evidence that there is more to late radiat ion injuries than delayed mitotic cell death.