Impact of angiotensin II type 2 receptor blockade on experimental radiation nephropathy. Radiat Res 2004 Mar;161(3):312-7
Date
02/26/2004Pubmed ID
14982483DOI
10.1667/rr3129Scopus ID
2-s2.0-2442684525 (requires institutional sign-in at Scopus site) 30 CitationsAbstract
In the rat, blockade of angiotensin II type 1 receptors diminishes the functional changes that occur after kidney irradiation. It has been hypothesized that some of the beneficial effects of angiotensin II type 1 blockers in renal disease are caused by a rise in angiotensin II that stimulates the angiotensin II type 2 receptor. If this hypothesis applied in this model, blockade of the type 2 receptor should exacerbate radiation nephropathy and/or counteract the beneficial effects of type 1 receptor blockade. To assess this hypothesis, rats were given total-body irradiation plus bone marrow transplantation and then treated for 12 weeks with a type 1 receptor blocker (L158,809), a type 2 blocker (PD123319), both blockers, or no blockers. Rats were assessed for renal function (proteinuria, hypertension, azotemia) and renal failure for up to 62 weeks. Contrary to the hypothesis, the type 2 blocker alone produced a temporary delay in the development of radiation nephropathy, and it substantially enhanced the efficacy of the type 1 blocker. This implies that both type 1 and type 2 angiotensin receptors need to be blocked to achieve the maximum level of prophylaxis of radiation nephropathy. We speculate that the beneficial effect of the angiotensin II type 2 receptor blocker is due to a reduction in radiation-induced renal cell proliferation or fibrosis.
Author List
Moulder JE, Fish BL, Cohen EPMESH terms used to index this publication - Major topics in bold
Angiotensin II Type 1 Receptor BlockersAngiotensin II Type 2 Receptor Blockers
Animals
Dose-Response Relationship, Drug
Drug Interactions
Imidazoles
Kidney Diseases
Kidney Function Tests
Male
Pyridines
Radiation Injuries, Experimental
Radiation Protection
Radiation Tolerance
Rats
Receptor, Angiotensin, Type 1
Receptor, Angiotensin, Type 2
Tetrazoles
Treatment Outcome
