LEUKOCYTE INFILTRATION AND ICAM-1 EXPRESSION IN 2-KIDNEY ONE-CLIP HYPERTENSION

How an increase in blood pressure, in and of itself, induces hypertens ive nephrosclerosis is unclear. In an earlier study we found that leuk ocyte infiltration, proximal tubular cell proliferation, matrix deposi tion 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 vas cular endothelium and tubular epithelium of unclipped kidneys at 4 wee ks. As a positive control, we examined the clipped kidney as well. We found that systolic blood pressure was significantly elevated in renov ascular hypertensive rats compared to sham-operated controls after 4 w eeks (198 +/- 5 mmHg vs 121 +/- 2 mmHg, P < 0.001). Furthermore, quant itative (densitometry) measurements showed that ICAM-1 expression on v ascular endothelium and on tubular cells was significantly increased i n unclipped kidneys compared to controls (P < 0.05). The same was true for monocyte and granulocyte infiltration (P < 0.05). These same vari ables were even more prominent in the clipped kidneys, compared to unc lipped and control kidneys (P < 0.05). Our data show that ICAM-1 is ex pressed in unclipped kidneys exposed to hypertension as well as in cli pped kidneys exposed to ischemia. We suggest that mechanical injury in duced by increased blood pressure is responsible for an inflammatory a dhesion molecule-mediated response and concomitant renal injury.