Role of the angiotensin II type-2 receptor in radiation nephropathy. Transl Res 2007 Aug;150(2):106-15
Date
07/28/2007Pubmed ID
17656330Pubmed Central ID
PMC2034340DOI
10.1016/j.trsl.2007.03.004Scopus ID
2-s2.0-34447542611 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
Experimental studies have shown that blockade of the angiotensin II type-1 (AT(1)) receptor is effective in the mitigation and treatment of radiation-induced chronic renal failure. Also, blockade of the angiotensin II type-2 (AT(2)) receptor with PD-123319 also had a modest, but reproducible, beneficial effect in experimental radiation nephropathy, and it might augment the efficacy of an AT(1) blocker (L-158,809). Those studies could not exclude the possibility that the effects of AT(2) blockade were nonspecific. The current studies confirm the efficacy of AT(2) blockade for mitigation of experimental radiation nephropathy but paradoxically find no detectable level of AT(2) receptor binding in renal membranes. However, the results of a bioassay showed that the circulating levels of the AT(2) blocker were orders-of-magnitude too low to block AT(1) receptors. The effect of AT(2) blockade in radiation nephropathy cannot be explained by binding to the AT(1) receptor, and the efficacy of the AT(1) blockade in the same model cannot be explained by unopposed overstimulation of the AT(2) receptor.
Author List
Cohen EP, Fish BL, Sharma M, Li XA, Moulder JEMESH terms used to index this publication - Major topics in bold
Angiotensin IIAngiotensin II Type 2 Receptor Blockers
Animals
Cell Line
Humans
Imidazoles
Kidney Diseases
Male
Mice
Pyridines
Radiation Injuries, Experimental
Rats
Receptor, Angiotensin, Type 2
Tetrazoles
Time Factors
