Angiotensin II receptor antagonists in the prevention of radiation nephropathy.
Angiotensin-converting enzyme (ACE) inhibitors can be used to prevent the development of radiation nephropathy. Current studies were designed to determine whether blocking the angiotensin II (AII) receptor, rather than preventing the creation of AII, would be effective in the prophylaxis of radiation nephropathy. Rats received 17 Gy total-body irradiation (TBI) in six fractions followed by syngeneic bone marrow transplantation (BMT). Prior to TBI the rats were randomized to groups receiving an ACE inhibitor (captopril), an AII type 1 (AT1) receptor antagonist (L-158,809) or no treatment. Renal function was assessed over 40 weeks, and a subset of animals were sacrificed for histopathology at 33 weeks. Renal function deteriorated progressively in animals receiving TBI alone, leading to renal failure by 34 weeks. Renal function was significantly better in animals receiving either captopril or L-158,809, and none of these animals had progressed to renal failure by 43 weeks. Analysis of both renal function and histopathology shows that the AII receptor antagonist is more effective than the ACE inhibitor in the prophylaxis of BMT nephropathy. This indicates that a reduction of activation of the AT1 receptor by AII, by itself, is sufficient for the prophylaxis of radiation nephropathy.
Moulder
J E
JE
Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, 53226, USA.
Fish
B L
BL
Cohen
E P
EP
Bonsib
S M
SM
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D007668:Kidney / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D013777:Tetrazoles / Q000494:pharmacology*; D014916:Whole-Body Irradiation
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D011837:Radiation-Protective Agents; D013777:Tetrazoles; C070967:L 158809; D002216:Captopril