Arterial damage precedes the development of interstitial damage in the nonclipped kidney of two-kidney, one-clip hypertensive rats.
BACKGROUND
The progression of damage in the renal cortex has not been investigated in the nonclipped kidney of the two-kidney, one-clip model of renal hypertension. In other hypertensive models, damage has been found to progress from the juxtamedullary cortex (JMC) and outward, which has been attributed to early vascular effects.


METHODS
The present study investigated the relation between perivascular deposition of collagen and structural damage after 16 and 24 weeks of hypertension in the nonclipped kidney in rats.


RESULTS
Periarterial collagen density in the kidney was significantly increased already 16 weeks after clipping, at that time tubulointerstitial damage was not evident. After 24 weeks of clipping, periarterial collagen was further increased, and tubulointerstitial damage had developed in the JMC, whereas the outer cortex was protected. Interstitial collagen was not significantly increased in any cortex part during the course of the experiment. Collagen type I a1 mRNA was increased in the JMC after 24 weeks, and α smooth muscle actin histochemistry and collagen type I a2 in-situ hybridization identified myofibroblasts around the arteries after 16 and 24 weeks as the major source of this increase.


CONCLUSIONS
Fibrosis in the nonclipped kidney of renal hypertensive rats starts around the juxtamedullary resistance vessels and then progresses in the JMC, whereas the outer cortex is protected. This suggests that pressure-induced injury to the vasculature attracts or activates fibroblasts in the perivascular area, which may allow damage to progress by impairing vessel function.
Renal Research Group, Institute of Medicine, University of Bergen, Bergen, Norway. trude.skogstrand@med.uib.no
Trude
T
Skogstrand
Sabine
S
Leh
Alexander
A
Paliege
Rolf K
RK
Reed
Bjørn E
BE
Vikse
Sebastian
S
Bachmann
Bjarne M
BM
Iversen
Michael
M
Hultström
D000818:Animals; D015153:Blotting, Western; D003094:Collagen / Q000378:metabolism; D006977:Hypertension, Renal / Q000473:pathology* / Q000503:physiopathology; D006978:Hypertension, Renovascular / Q000473:pathology* / Q000503:physiopathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D007672:Kidney Cortex / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D013525:Surgical Instruments
D003094:Collagen