Renal proliferative and phenotypic changes in rats with two-kidney, one-clip Goldblatt hypertension.
Angiotensin II (AII) is a vasoconstrictive peptide with hypertrophic and mitogenic effects on many cell types. Previous studies have shown that in vivo administration of AII in rats results in proliferation of, and phenotypic changes in, many renal cell populations, but in doses also causing hypertension. Thus, it was not possible to differentiate nonhemodynamic from hypertensive effects of AII. Therefore, we studied rats with renin-dependent, AII-mediated hypertension (the two-kidney, one-clip Goldblatt model; mean systolic blood pressure 238 +/- 48 v 140 +/- 6 mm Hg in sham-operated controls). The unclipped kidneys, which were exposed to high blood pressure, developed significant glomerular and tubulointerstitial injury, tubulointerstitial cell proliferation, dense focal interstitial monocyte-macrophage influx, increased deposition of types I and IV collagen, as well as increased cellular expression of desmin and actin, in tubulointerstitial areas when examined at 11 weeks. In contrast, clipped kidneys, protected from hypertension but with high local renin expression, had minimal abnormalities. These studies suggest that in this model increased renin, and presumably AII, does not mediate significant proliferative or phenotypic changes in the kidney in the absence of hypertension at 11 weeks.
Eng
E
E
Department of Medicine, University of Washington, Seattle 98195.
Veniant
M
M
Floege
J
J
Fingerle
J
J
Alpers
C E
CE
Menard
J
J
Clozel
J P
JP
Johnson
R J
RJ
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D002455:Cell Division / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005355:Fibrosis / Q000473:pathology; D006978:Hypertension, Renovascular / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D007962:Leukocytes / Q000378:metabolism; D008264:Macrophages / Q000502:physiology; D008297:Male; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000378:metabolism / Q000502:physiology
D003598:Cytoskeletal Proteins; D000804:Angiotensin II; D012083:Renin