Renoprotective effects of azelnidipine by improvements of renal microcircuration *
Hypoxia induced tubulointerstitial injury is proposed to be associated with a progression of renal diseases. Tubulointerstitial hypoxia is caused by loss of peritublar capillary（PTC）blood flow. Therefore, maintenance of the blood flow in PTC may protect from loss of renal function. A long acting calcium channel blocker, azelnidipine, is useful in progressive renal disease. However, this mechanism is not elucidated well. The present study was made to elucidate whether azelnidipine, a new long acting calcium channel blocker, kept the blood flow in PTC and improved a tubulointerstitial injury caused by angiotensin II（AII）in rats. At first, PTC blood flows in WKY rats were monitored using a pencil-lens interval microscope before and after intravenous AII（30ng/min）infusion with or without azelnidipine（0.1mg/kg）. PTC blood flow was reduced after AII infusion. However, after bolus injection of azelnidipine, PTC blood flow was improved. Next, WKY rats were treated by chronic infusion of AII（500ng/kg/min）via an osmotic minipump with or without the azelnidipine（30mg/kg/day, orally）for 14 days. Tubulointerstitial damages（PTC loss, interstitial fibrosis, tubular atrophy）were observed in chronic AII treated rat kidney. These changes were associated with the hypoxic conditions measured by hypoxia biomarkers（intracellular accumulation of hypoxyprobe-1 adducts and expression of hypoxia inducible factor-1 alpha protein）. These tublointerstitial injuries in AII infused rats were not blocked completely but reduced by azelnidipine treatment. The area of hypoxic condition in the kidney was also improved by azelnidipine. These findings suggest that azelnidipine may increase PTC blood flow and improve a renal hypoxia and tublointerstitial injury by AII. (Accepted on October 19，2004)
