Peritubular capillary loss is ameliorated by ramipril or valsartan treatment.
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.
Zhang
Bin
B
Department of Nephrology, Guangdong Provincial People's Hospital, Nanfang Medical University, Guangzhou, China.
Chen
Nan
N
Shi
Wei
W
Wang
Weiming
W
Shi
Hao
H
Yu
Haijin
H
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002196:Capillaries / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D007684:Kidney Tubules / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D000959:Antihypertensive Agents; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; D000068756:Valsartan; D014633:Valine; D017257:Ramipril