The renin-angiotensin system in experimental radiation nephropathy.
Irradiation of the kidneys is followed by a well-defined sequence of changes leading eventually to kidney failure. In the rat, inhibition of angiotensin-converting enzyme or blockade of angiotensin II receptors can prevent the structural and functional changes that occur after kidney irradiation. These interventions are particularly effective between 3 and 10 weeks after irradiation. However, in a series of studies with the rat model we failed to find any evidence that the renin-angiotensin system (RAS) is activated in the first 10 weeks after kidney irradiation. First, if the RAS was activated during this interval, one would expect hypertension followed by proteinuria and azotemia. However, hypertension is significant only at the end of this period and is preceded by significant proteinuria and azotemia. This evolution is not in favor of an obviously activated RAS during the 3- to 10-week postirradiation interval that is critical for interventions aimed at the RAS. Second, plasma renin activity and active plasma renin protein concentrations are not significantly increased over the first 10 weeks after irradiation. Third, whole-blood and intrarenal angiotensin II levels are not increased and may even be decreased over this interval. This last observation is particularly important because the assay used is sensitive enough to detect the effects of dietary salt manipulation. We hypothesize that even the normal activity of the RAS contributes to injury after kidney irradiation, possibly by supporting the proliferation of cells that carry potentially lethal radiation injuries.
Cohen
Eric P
EP
Department of Medicine, Division of Nephrology, Medical College of Wisconsin, Froedtert Memorial Lutheran Hospital, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA. ecohen@mcw.edu
Fish
Brian L
BL
Moulder
John E
JE
D000818:Animals; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007668:Kidney / Q000737:chemistry / Q000503:physiopathology / Q000528:radiation effects*; D011507:Proteinuria / Q000503:physiopathology; D051381:Rats; D011945:Receptors, Angiotensin / Q000032:analysis / Q000097:blood; D051437:Renal Insufficiency / Q000503:physiopathology*; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology / Q000528:radiation effects*; D014511:Uremia / Q000503:physiopathology
D011945:Receptors, Angiotensin; D012083:Renin