Peritubular capillary loss is ameliorated by ramipril or valsartan treatment

Microcirculation. 2008 May;15(4):337-48. doi: 10.1080/10739680701743540.

Abstract

Objective: To identify the preservation of peritubular capillaries conferred by ramipril or valsartan treatment as an additional mechanism for their renoprotection.

Methods: The effect of ramipril or valsartan on peritubular capillaries was investigated in a remnant kidney model using male Sprague-Dawley rats sacrificed post-operatively at 3, 6 and 12 weeks respectively. Peritubular capillaries and tubulointerstitial hypoxia in untreated remnant kidney rats (n = 26), remnant kidney rats treated with ramipril (n = 22, 0.5 mg/kg/day), valsartan (n = 22, 30 mg/kg/day) or amlodipine (n = 22, 30 mg/kg/day) and sham-operated rats (n = 22) were assessed by CD141 and HIF-1alpha staining.

Results: Ramipril or valsartan significantly preserved the peritubular capillaries as well as renal function (p < 0.01). Tubulointerstitial hypoxia and tubular TGF-beta expression were noted well before the development of tubulointerstitial damage. The gentler slope of the relationship between HIF-1alpha scores and peritubular capillary density in individual rats was noted in both ramipril-treated and valsartan-treated groups compared to the untreated remnant kidney group (p < 0.05).

Conclusions: Amelioration of peritubular capillary loss and subsequent tubular hypoxia by ramipril or valsartan treatment should be interpreted as an alternative type of their renoprotection, one which also implies a novel focus for clinical intervention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology*
  • Capillaries / metabolism
  • Gene Expression Regulation / drug effects
  • Hypoxia / drug therapy*
  • Hypoxia / metabolism
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis
  • Kidney Tubules / blood supply*
  • Kidney Tubules / metabolism
  • Male
  • Microcirculation / drug effects
  • Ramipril / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Tetrazoles / pharmacology*
  • Transforming Growth Factor beta / biosynthesis
  • Valine / analogs & derivatives*
  • Valine / pharmacology
  • Valsartan

Substances

  • Antihypertensive Agents
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Tetrazoles
  • Transforming Growth Factor beta
  • Valsartan
  • Valine
  • Ramipril