Faculty Collaboration Database

Angiotensin II blockade reduces radiation-induced proliferation in experimental radiation nephropathy. Radiat Res 2002 Apr;157(4):393-401

Date

03/15/2002

Pubmed ID

11893241

DOI

10.1667/0033-7587(2002)157[0393:aibrri]2.0.co;2

Scopus ID

2-s2.0-0036210270 (requires institutional sign-in at Scopus site)   24 Citations

Abstract

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.

Author List

Moulder JE, Fish BL, Regner KR, Cohen EP

Author

Kevin R. Regner MD Interim Chair, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Angiotensin Receptor Antagonists
Animals
Antihypertensive Agents
Cell Division
Disease Models, Animal
Imidazoles
Kidney
Kidney Diseases
Kidney Glomerulus
Kidney Tubules
Proliferating Cell Nuclear Antigen
Rats
Receptor, Angiotensin, Type 1
Tetrazoles
Time Factors