Leukocyte infiltration and ICAM-1 expression in two-kidney one-clip hypertension.
How an increase in blood pressure, in and of itself, induces hypertensive nephrosclerosis is unclear. In an earlier study we found that leukocyte infiltration, proximal tubular cell proliferation, matrix deposition and interstitial fibrosis occur in the unclipped kidney of 2 K 1 C Goldblatt hypertensive rats. In this study we tested the hypothesis that the cell surface adhesion molecule ICAM-1 is expressed on the vascular endothelium and tubular epithelium of unclipped kidneys at 4 weeks. As a positive control, we examined the clipped kidney as well. We found that systolic blood pressure was significantly elevated in renovascular hypertensive rats compared to sham-operated controls after 4 weeks (198 +/- 5 mmHg vs 121 +/- 2 mmHg, P < 0.001). Furthermore, quantitative (densitometry) measurements showed that ICAM-1 expression on vascular endothelium and on tubular cells was significantly increased in unclipped kidneys compared to controls (P < 0.05). The same was true for monocyte and granulocyte infiltration (P < 0.05). These same variables were even more prominent in the clipped kidneys, compared to unclipped and control kidneys (P < 0.05). Our data show that ICAM-1 is expressed in unclipped kidneys exposed to hypertension as well as in clipped kidneys exposed to ischemia. We suggest that mechanical injury induced by increased blood pressure is responsible for an inflammatory adhesion molecule-mediated response and concomitant renal injury.
Haller
H
H
Franz Volhard Clinic, Humboldt University of Berlin, Germany.
Park
J K
JK
Dragun
D
D
Lippoldt
A
A
Luft
F C
FC
D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006098:Granulocytes / Q000473:pathology; D006978:Hypertension, Renovascular / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007962:Leukocytes / Q000473:pathology*; D008297:Male; D009000:Monocytes / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D018799:Intercellular Adhesion Molecule-1