Azelnidipine exerts renoprotective effects by improvement of renal microcirculation in angiotensin II infusion rats

Nephrol Dial Transplant. 2009 Dec;24(12):3651-8. doi: 10.1093/ndt/gfp407. Epub 2009 Aug 7.

Abstract

Background: Hypoxia-induced tubulointerstitial injury caused by loss of peritubular capillary (PTC) blood flow may be associated with progressive renal disease. Therefore, the maintenance of blood flow in PTCs may protect against loss of renal function. A long-acting calcium channel blocker, azelnidipine, has been shown to be useful in the treatment of progressive renal disease. However, its mechanism of action remains unclear. The aim of the present study was to elucidate whether azelnidipine maintains PTC blood flow and to compare it to nifedipine in its ability to improve tubulointerstitial injury caused by angiotensin II (AII) infusion in rats.

Methods: PTC blood flow was initially monitored using a pencil-lens interval microscope before and after intravenous AII (30 ng/kg/min) infusion with or without azelnidipine (10 microg/kg/min). Next, Wistar rats were treated with chronic infusion of AII (500 ng/kg/min) via an osmotic minipump with or without azelnidipine (3 mg/kg/day, orally) or nifedipine (60 mg/kg/day, orally) for 14 days, and tubulointerstitial damage (PTC loss, interstitial fibrosis, tubular atrophy) was examined.

Results: PTC blood flow was reduced after AII infusion but improved after a bolus injection of azelnidipine. Tubulointerstitial damage observed in chronically AII-treated kidneys was associated with hypoxic conditions, as indicated by the measurement of hypoxia biomarkers (intracellular hypoxyprobe-1 adducts). These tubulointerstitial injuries in AII-infused rats were more effectively reduced by azelnidipine than by nifedipine. The area showing hypoxic conditions in the kidney was also more reduced with azelnidipine than nifedipine treatment.

Conclusions: Azelnidipine may increase PTC blood flow and improve renal hypoxia and tubulointerstitial injury induced by AII infusion.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / administration & dosage
  • Animals
  • Azetidinecarboxylic Acid / analogs & derivatives*
  • Azetidinecarboxylic Acid / therapeutic use
  • Calcium Channel Blockers / therapeutic use*
  • Dihydropyridines / therapeutic use*
  • Infusions, Intravenous
  • Male
  • Microcirculation / drug effects*
  • Nephritis, Interstitial / physiopathology*
  • Nephritis, Interstitial / prevention & control*
  • Nifedipine / therapeutic use*
  • Rats
  • Rats, Wistar
  • Renal Circulation / drug effects*

Substances

  • Calcium Channel Blockers
  • Dihydropyridines
  • Angiotensin II
  • Azetidinecarboxylic Acid
  • Nifedipine
  • azelnidipine