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-1α staining.
Results: Ramipril or valsartan significantly preserved the peritubular capillaries as well as renal function (p < 0.01). Tubulointerstitial hypoxia and tubular TGF-β expression were noted well before the development of tubulointerstitial damage. The gentler slope of the relationship between HIF-1α 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.
This work was supported by Science & Technology Commission of Shanghai Municipality grant (No. 03JC14084), Shanghai Board of Health grant (No. 983009) and Guangdong Research Project (No. 2004B30701007).