Leukocyte infiltration and ICAM-1 expression in two-kidney one-clip hypertension

How an increase in blood pressure, in and of itself, induces hypertensivenephrosclerosis is unclear. In an earlier study we found that leukocyteinfiltration, proximal tubular cell proliferation, matrix deposition andinterstitial fibrosis occur in the unclipped kidney of 2 K 1 C Goldblatthypertensive rats. In this study we tested the hypothesis that the cellsurface adhesion molecule ICAM-1 is expressed on the vascular endotheliumand tubular epithelium of unclipped kidneys at 4 weeks. As a positivecontrol, we examined the clipped kidney as well. We found that systolicblood pressure was significantly elevated in renovascular hypertensive ratscompared to sham-operated controls after 4 weeks (198 ± 5 mmHgvs 121 ± 2 mmHg, P<0.001). Furthermore, quantitative (densitometry) measurementsshowed that ICAM-1 expression on vascular endothelium and on tubular cellswas significantly increased in unclipped kidneys compared to controls(P <0.05). The same was true for monocyte andgranulocyte infiltration (P <0.05). These samevariables were even more prominent in the clipped kidneys, compared tounclipped and control kidneys (P < 0.05). Ourdata show that ICAM-1 is expressed in unclipped kidneys exposed tohypertension as well as in clipped kidneys exposed to ischemia. We suggestthat mechanical injury induced by increased blood pressure is responsiblefor an inflammatory adhesion molecule-mediated response and concomitantrenal injury.