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H. Takahashi, W. Yaqiong, A. Iriyama, R. Obata, Y. Inoue, A. Numabe, Y. Yanagi, Y. Tamaki, M. Araie, Y. Uehara; Leukocyte Adhesion to Retinal Blood Vessel is Correlated With the Renal Damage of Dahl Salt-Sensitive Rat. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3211.
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© ARVO (1962-2015); The Authors (2016-present)
Dahl salt-sensitive rats (DS) are a rat model for salt-dependent hypertension with organ damage. However, the mechanisms of their susceptibility to hypertensive organ damage remain to be elucidated. Using DS rats, we investigated whether the leukocyte adhesion to retinal blood vessel is correlated with kidney damage and the expression of adhesion molecule in the blood.
A total of thirty 4-week-old DS were fed with either a low salt (0.3%NaCl) diet or with a high salt (8%NaCl) diet for 20 days and subjected to analysis. DS fed with a high salt diet were assigned to untreated control (non-treated control-group), treatment group with 3-hydroxy-3-methylglutaryl-CoA reductase fluvastatin (2.5mg/kgBW/day) for the first 10-day period (early-treatment group), or for the late 10-day period (late-treatment group), or for 20 days (whole-treatment group). Adhesion of leukocyte, stained by acridine orange (0.1% w/v), to the retinal blood vessel (R-WBC) was quantitatively determined using the scanning laser ophthalmoscope (Rodenstock, Ottobrunn, Germany). Kidney damage was assessed by urinary protein excretion levels (UpV) and morphological glomerular sclerosis (GS) was assessed by hisitological analysis. Serum concentrations of monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1) and tumor necrosis factor-a (TNF-a) were determined by ELISA.
Systolic blood pressure (SBP) of the control group increased to 220 mmHg 3 weeks after salt-loading (p<0.0001 vs 0.3%NaCl group), UpV quickly increased to 819mg/day (p<0.0001 vs 0.3%NaCl group)and GS exacerbated (225 vs 82 in 0.3%NaCl group). Serum MCP-1 increased significantly (1255 pg/nl vs 685 in 0.3%NaCl group, p<0.005). Early treatment with fluvastatin significantly inhibited the upregulation of SBP, UpV and MCP-1. On the other hand, late-treatment and whole-treatment group exhibited a decrease in GS score (p<0.05). Leukocyte adhesion was well correlated with GS and MCP-1 (p<0.05) by stepwise multiple regression analysis.
GS score and MCP-1 expression were decreased by early fluvastatin treatment. Leukocyte adhesion to the retinal vessels was well correlated with the GS and the serum levels of MCP-1. These suggest that kidney protection by fluvastatin is mediated in part through inhibition of MCP-1 and leukocyte adhesion onto small vessels.
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