Angiotensin II receptor antagonists in the treatment and prevention of radiation nephropathy.

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.