Angiotension II receptor 1 blocker modifies the expression of apoptosis-related proteins and transforming growth factor-beta1 in prostate tissue of spontaneously hypertensive rats.
OBJECTIVE
To assess whether angiotensin II (Ang II), important in hypertension and highly expressed in benign prostatic hyperplasia (BPH), is involved in prostate growth, by analysing changes in the histological composition, tissue apoptotic status and level of transforming growth factor-beta1 (TGFbeta1) induced by an Ang II type 1 receptor blocker, losartan, in the prostates of spontaneously hypertensive (SH) rats.


METHODS
We assessed four groups of six rats each: normotensive Wistar-Kyoto counterparts of SH rats; untreated SH rats; SH rats given low-dose losartan (10 mg/kg/day for 10 weeks); and SH given high-dose losartan (30 mg/kg/day for 10 weeks). We evaluated the histological composition and expression of TGFbeta1 and apoptosis-related proteins, i.e. Bax and the 116-kDa poly (adenosine diphosphate-ribose) polymerase (PARP), by Western blotting in the rat prostate ventral lobes.


RESULTS
Compared with Wistar-Kyoto rats, untreated SH rats had a significantly increased epithelium component in the prostate (P < 0.01), but with losartan treatment, SH rats showed less of the epithelium component than untreated rats (P < 0.01 for both low- and high-dose losartan). Western-blot analysis showed a significantly increased level of Bax in high-dose losartan-treated rats (P < 0.01). The expression of 116 kDa PARP was also decreased in these rats (P < 0.01), which suggests increased caspase-3 activity. In addition, TGFbeta1 levels were significantly elevated in high-dose losartan-treated rats (P < 0.01).


CONCLUSIONS
These results show that losartan can induce apoptosis of prostate epithelium and increase the TGFbeta1 expression in SH rats, suggesting that Ang II stimulation might be involved in the pathogenesis of BPH, which might correlate with the regulation of TGFbeta1 expression.
Yu
Wei
W
Department of Urology, Peking University First Hospital, Peking University, and Department of Physiology and Pathophysiology, Peking University, China.
Zhao
Ya-Yuan
YY
Zhang
Zhi-Wen
ZW
Guo
Ying-Lu
YL
Jin
Jie
J
D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism