Angiotensin II infusion exacerbates radiation nephropathy

We hypothesized that angiotensin II will exacerbate radiation nephropathy in a time-specific manner, Experimental radiation nephropathy is treatable with angiotensin-converting enzyme inhibition or angiotensin II (All) receptor blockers, These interventions are particularly important between 3 and in weeks after irradiation. We therefore undertook studies in which All infusions were given at particular intervals after irradiation. Rats received total body irradiation (TBI) plus syngeneic bone marrow transplantation followed (or not) by All infusion at 200 or 400 ng/kg/min, Infusions were given from 0 to 4 or 4 to 8 weeks after irradiation, An additional group was unirradiated but infused at 800 ng/kg/min for 8 weeks. Kidney function was assessed over 26 weeks, and histology was evaluated after the animals were killed. All infusion alone did not cause azotemia, There was transient hypertension during All infusion at 800 ng/kg/min but only minor histologic injury. Irradiation caused azotemia and hypertension, which were not exacerbated by AII infusion at 200 ng/kg/min, Irradiation plus All infusion at 400 ng/kg/min from 4 to 8 weeks after TBI caused significantly greater azotemia than irradiation alone or irradiation with All infusion from 0 to 4 weeks, The blood pressure was higher in irradiated rats infused with All from 4 to 8 weeks. Arteriolar fibrinoid necrosis was a prominent feature in kidneys of rats infused with All from 4 to 8 weeks after TBI. The worsening of radiation nephropathy by All infusion from 4 to 8 weeks after irradiation strongly supports the idea of specific and sequential events in the pathogenesis of kidney failure in this model. Hypertension may play a role in these events in addition to the effect of All alone. The occurrence of arteriolar fibrinoid necrosis in the irradiated, 4-to-8-week-infused animals suggests that vascular injury during that interval determines later outcome.