EARLY INTERSTITIAL CHANGES IN HYPERTENSION-INDUCED RENAL INJURY

To elucidate the mechanisms of hypertensive renal injury, we investiga ted the time course and extent of changes in matrix composition, as we ll as cell proliferation and infiltration in two-kidney, one clip rats . The nonclipped kidneys from hypertensive and sham-operated control r ats (n=5 to 10 in each group) were studied at 7, 14,21, and 28 days af ter clipping. Systolic blood pressure was elevated by day 7 (154+/-3 v ersus 111+/-4 mm Hg in sham group, P<.001, n=10 each). Hypertension re sulted in an early expansion of the interstitial volume by 37%, wherea s hypertensive vascular changes and glomerular injury did not become e vident until day 21. Immunofluorescence studies revealed an early inte rstitial accumulation of collagens I, III, IV, V, VI, and fibronectin by day 7. In contrast, the glomeruli showed a mild to moderate increas e in collagens I, III, IV, V, laminin, and fibronectin but not collage n VI later in the established phase of hypertension. Staining for prol iferating cell nuclear antigen as a marker of cell replication was inc reased in tubular epithelial but not interstitial or glomerular cells. A progressive infiltration of macrophages (16+/-2 versus 9+/-1 ED1+ c ells/mm2, P<.05, n=6) and T lymphocytes (93+/-15 versus 74+/-7 CD4+ ce lls/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 ma trix 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.