title: [Inhibitory effect of losartan on prostatic hyperplasia in spontaneous hypertension rats and its pathophysiological mechanism].
abstract: OBJECTIVE
  To investigate the effect of losartan on prostatic hyperplasia in spontaneous hypertension rats (SHRs) and its pathophysiological mechanism.
  
  
  METHODS
  We randomly divided 36 male SHRs into three groups of equal number to be treated intragastrically with high-dose losartan (30 mg per kg per d), low-dose losartan (15 mg per kg per d) and distilled water (control group). After 6 weeks of intervention, we measured the body weight and tail artery blood pressure of the rats and compared them with the baseline data. We collected blood from the heart for determination of the levels of serum angiotensin II (Ang II), insulin-like growth factor-1 (IGF-1) and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay (ELISA), and harvested their prostates for measurement of their weight, observation of the tissue ultrastructures under the electron microscope and detection of the expression of endothelial nitric oxide synthase (eNOS) in the prostate tissue by immunohistochemistry.
  
  
  RESULTS
  Compared with the control group, the low- and high-dose losartan groups showed significant decreases in systolic blood pressure ([203.75 +/- 10.28] vs [184.54 +/- 16.90] mmHg, P = 0.013; [203.75 +/- 10.28] vs [166.88 +/- 14.74] mmHg, P = 0.001) and diastolic blood pressure ([151.58 +/- 9.96] vs [136.71 +/- 14.28] mmHg, P = 0.022; [151.58 +/- 9.96] vs [122.71 +/- 11.56] mmHg, P < 0.001) of the lower tail artery after treatment, as well as in the prostate weight ([0.73 +/- 0.08] vs [0.64 +/- 0.10] mg, P = 0.011; [0.73 +/- 0.08 ] vs [0.50 +/- 0.17] mg, P < 0.001). Electron microscopy revealed edema of the basal and columnar epithelial cells, concentrated and marginated heterochromatin and widened nuclear gap of interstitial fibroblast nuclei, and reduced mitochondria and endoplasmic reticula in the low-dose losartan group, and even more obvious in the high-dose group. The level of serum Ang II was remarkably higher in the low- and high-dose losartan groups than in the control ([61.32 +/- 2.49] vs [54.85 +/- 7.20] pg/ml, P = 0.021; [65.49 +/- 6.78] vs [54.85 +/- 7.20] pg/ml, P < 0.001]) , that of serum IGF-1 was lower in high-dose losartan than in the control group ([1.50 +/- 0.11] vs [1.60 +/- 0.10] ng/ml, P = 0.03), but the serum IL-6 levels exhibited no significant differences among the three groups. The expression of eNOS in the prostate tissue was significantly higher in the losartan groups than in the controls (P = 0.022), even higher in the high-dose than in the low-dose group.
  
  
  CONCLUSIONS
  Losartan can suppress the progression of prostate hyperplasia in spontaneous hypertension rats by inhibiting RAS, IGF-1 and angiogenesis.
authors.affiliation: The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Shen
authors.forename: Li-Ni
authors.initials: LN
authors.lastname: Dong
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Zhang
authors.forename: Xiao-Kun
authors.initials: XK
authors.lastname: Zhao
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Zeng
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Qu
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D000959:Antihypertensive Agents; D015850:Interleukin-6; D000804:Angiotensin II; D007334:Insulin-Like Growth Factor I; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019808:Losartan