[Effect of perindopril on renal interstitial fibrosis of hypertension in rats].
OBJECTIVE
To explore the effect of perindopril on renal interstitial fibrosis of spontaneously hypertensive rats and on the expression of transforming growth factor-beta1.


METHODS
Spontaneously hypertensive rats at the age of 9 weeks were randomly assigned to 2 groups: Spontaneously hypertensive rats (SHR, vehicle once daily, n = 10) and Treament-SHR (T-SHR, perindopril, 4 mg/(kg x d), per day PO, n = 10). Wistar-Kyoto rats (WKY, n = 7) were served as controls. After 10 weeks of treatment, the serum concentration of TGF-beta1, collagen type I, III and TGF-beta1 in the renal interstitum and renal mRNA levels of TGF-beta1 were detected.


RESULTS
There were no significant differences in the serum TGF-beta1 levels among the 3 groups (P > 0.05). Immunohistochemical studies revealed a significant interstitial accumulation of collagens I, III and TGF-beta1 in SHR compared with those in WKY (P < 0.01 or P < 0.05). These changes in SHR were significantly ameliorated by the administration of perindopril (P < 0.01 or P < 0.05). In SHR, renal TGF-beta1 mRNA expression was increased significantly compared with that in WKY (P < 0.01), but perindopril decreased it to the normal levels of WKY (P > 0.05). The increased expression of TGF-beta1 was blocked by perindopril. The expressions of collagens I and III in renal interstitum significantly correlated with the accumulation of TGF-beta1 in the renal (r = 0. 734, r = 0.762, respectively; P < 0.01).


CONCLUSIONS
The tubulointerstitial fibrosis of spontaneously hypertensive rats is mediated by an increased level of TGF-beta1 in the renal tissue, and perindopril may decrease the expression of TGF-beta1 to ameliorate the tubulointerstitial fibrosis.
Xu
Hui
H
Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008, China.
Tao
Li-Jian
LJ
Sun
Ming
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics; D024061:Collagen Type III / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007668:Kidney / Q000378:metabolism; D008297:Male; D009400:Nephrosclerosis / Q000188:drug therapy* / Q000378:metabolism; D020913:Perindopril / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D053773:Transforming Growth Factor beta1
D000806:Angiotensin-Converting Enzyme Inhibitors; D024042:Collagen Type I; D024061:Collagen Type III; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D020913:Perindopril