Angiotensin II blockade reduces radiation-induced proliferation in experimental radiation nephropathy.
Total-body irradiation or renal irradiation is followed by a well-defined sequence of changes in renal function leading eventually to renal failure. Previous studies in a rat model have shown that inhibition of angiotensin-converting enzyme or blockade of angiotensin II receptors can prevent the structural and functional changes that occur after renal irradiation, and that these interventions are particularly important between 3 and 10 weeks after irradiation. We have now shown that in the same rat model, total-body irradiation induces proliferation of renal tubular cells (i.e., an increase in the number of cells staining positive for proliferating cell nuclear antigen) within 5 weeks after irradiation. Treatment with an angiotensin II receptor blocker delays this radiation-induced tubular proliferation and decreases its magnitude. Renal radiation also induces proliferation of glomerular cells, but the relative increase in glomerular proliferation is not as great as that seen in renal tubular cells, and the increase is not delayed or decreased by treatment with an angiotensin II receptor blocker. We hypothesize that angiotensin II receptor blockers exert their beneficial effect in radiation nephropathy by delaying the proliferation (and hence the eventual mitotic death) of renal tubular cells that have been genetically crippled by radiation.
Moulder
John E
JE
Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. jmoulder@mcw.edu
Fish
Brian L
BL
Regner
Kevin R
KR
Cohen
Eric P
EP
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D004195:Disease Models, Animal; D007093:Imidazoles / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects*; D007674:Kidney Diseases / Q000473:pathology*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D018809:Proliferating Cell Nuclear Antigen; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; C070967:L 158809