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1 March 2004 Impact of Angiotensin II Type 2 Receptor Blockade on Experimental Radiation Nephropathy
John E. Moulder, Brian L. Fish, Eric P. Cohen
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Abstract

Moulder, J. E., Fish, B. L. and Cohen, E. P. Impact of Angiotensin II Type 2 Receptor Blockade on Experimental Radiation Nephropathy. Radiat. Res. 161, 312–317 (2004).

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.

John E. Moulder, Brian L. Fish, and Eric P. Cohen "Impact of Angiotensin II Type 2 Receptor Blockade on Experimental Radiation Nephropathy," Radiation Research 161(3), 312-317, (1 March 2004). https://doi.org/10.1667/RR3129
Received: 29 July 2003; Accepted: 1 October 2003; Published: 1 March 2004
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