Angiotensin II infusion exacerbates radiation nephropathy

We hypothesized that angiotensin II will exacerbate radiation nephropathy i n a time-specific manner, Experimental radiation nephropathy is treatable w ith angiotensin-converting enzyme inhibition or angiotensin II (All) recept or blockers, These interventions are particularly important between 3 and i n weeks after irradiation. We therefore undertook studies in which All infu sions were given at particular intervals after irradiation. Rats received t otal body irradiation (TBI) plus syngeneic bone marrow transplantation foll owed (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 uni rradiated but infused at 800 ng/kg/min for 8 weeks. Kidney function was ass essed over 26 weeks, and histology was evaluated after the animals were kil led. All infusion alone did not cause azotemia, There was transient hyperte nsion 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/k g/min from 4 to 8 weeks after TBI caused significantly greater azotemia tha n 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 radiati on 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 fibri noid necrosis in the irradiated, 4-to-8-week-infused animals suggests that vascular injury during that interval determines later outcome.