Hypertension, Vol 22, 754-765, Copyright © 1993 by American Heart Association
M Mai, H Geiger, KF Hilgers, R Veelken, JF Mann, J Dammrich and FC Luft
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.
ARTICLES
Early interstitial changes in hypertension-induced renal injury
Department of Internal Medicine-Nephrology, University of Erlangen, Germany.
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