Early interstitial changes in hypertension-induced renal injury.
To elucidate the mechanisms of hypertensive renal injury, we investigated the time course and extent of changes in matrix composition, as well as cell proliferation and infiltration in two-kidney, one clip rats. The nonclipped kidneys from hypertensive and sham-operated control rats (n = 5 to 10 in each group) were studied at 7, 14, 21, and 28 days after clipping. Systolic blood pressure was elevated by day 7 (154 +/- 3 versus 111 +/- 4 mm Hg in sham group, P < .001, n = 10 each). Hypertension resulted in an early expansion of the interstitial volume by 37%, whereas hypertensive vascular changes and glomerular injury did not become evident until day 21. Immunofluorescence studies revealed an early interstitial accumulation of collagens I, III, IV, V, VI, and fibronectin by day 7. In contrast, the glomeruli showed a mild to moderate increase in collagens I, III, IV, V, laminin, and fibronectin but not collagen VI later in the established phase of hypertension. Staining for proliferating cell nuclear antigen as a marker of cell replication was increased in tubular epithelial but not interstitial or glomerular cells. A progressive infiltration of macrophages (16 +/- 2 versus 9 +/- 1 ED1+ cells/mm2, P < .05, n = 6) and T lymphocytes (93 +/- 15 versus 74 +/- 7 CD4+ cells/mm2, n = 8) in the cortical interstitium had already occurred by day 7. On the other hand, only macrophages increased in number within the glomeruli. Thus, renovascular hypertension leads to an early tubular cell proliferation, mononuclear cell recruitment, and deposition of matrix proteins primarily within the interstitium. We conclude that the injury producing nephrosclerosis in this model extends far beyond the glomeruli. Both the tubules and the interstitium are actively involved and may be the more important initial sites of injury.
Mai
M
M
Department of Internal Medicine-Nephrology, University of Erlangen, Germany.
Geiger
H
H
Hilgers
K F
KF
Veelken
R
R
Mann
J F
JF
Dämmrich
J
J
Luft
F C
FC
D000818:Animals; D001160:Arterioles / Q000473:pathology; D001794:Blood Pressure; D001835:Body Weight; D002455:Cell Division; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D005353:Fibronectins / Q000032:analysis / Q000378:metabolism; D006321:Heart / Q000033:anatomy & histology / Q000503:physiopathology; D006978:Hypertension, Renovascular / Q000473:pathology* / Q000503:physiopathology*; D007668:Kidney / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D007797:Laminin / Q000032:analysis / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D012083:Renin / Q000097:blood; D013997:Time Factors; D014508:Urea / Q000097:blood
D005353:Fibronectins; D007797:Laminin; D014508:Urea; D003094:Collagen; D012083:Renin