Therapeutic effects of losartan on prostatic hyperplasia in spontaneously hypertensive rats

Life Sci. 2021 Feb 1:266:118924. doi: 10.1016/j.lfs.2020.118924. Epub 2020 Dec 19.

Abstract

Aims: We investigated the therapeutic effects of losartan, an angiotensin II type 1 receptor blocker, on prostatic hyperplasia in spontaneously hypertensive rats (SHRs).

Main methods: Male SHRs (age, 36 weeks) were perorally treated with losartan (3 or 10 mg·kg-1) or vehicle once daily for 18 weeks. Age-matched Wistar Kyoto rats (WKYs) were used as vehicle-treated controls (n = 8). The effects of losartan were evaluated by analyzing prostate weight, blood pressure, and prostatic blood flow. The tissue malondialdehyde (MDA), interleukin-6 (IL-6), and basic fibroblast growth factor (bFGF) levels were measured. Histological analysis for the ventral prostate involved hematoxylin and eosin staining and TdT-mediated dUTP nick-end labeling (TUNEL) assay.

Key findings: Compared to the vehicle-treated WKYs, the vehicle-treated SHRs had significantly higher prostate weight, prostate weight/body weight ratio (PBR), blood pressure, glandular epithelial area, and tissue MDA, IL-6, and bFGF levels in the ventral prostate and lower prostatic blood flow. Treatment with losartan caused significant recovery of blood flow and decreased PBR and glandular epithelial area as well as tissue MDA, IL-6, and bFGF levels in the SHR ventral prostate without affecting blood pressure. High-dose losartan significantly decreased blood pressure and increased TUNEL-positive cells in the ventral prostate in SHRs.

Significance: Chronic losartan treatment could ameliorate prostatic hyperplasia via recovery of reduced prostatic blood flow and induction of apoptosis in the ventral prostate in SHRs. Losartan might have therapeutic effects on not only hypertension but also prostatic hyperplasia in humans.

Keywords: Angiotensin II type 1 receptor blocker; Benign prostatic hyperplasia; Losartan; Spontaneously hypertensive rats; Ventral prostate.

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology*
  • Blood Pressure
  • Hypertension / complications*
  • Losartan / pharmacology*
  • Male
  • Malondialdehyde / metabolism
  • Oxidative Stress
  • Prostatic Hyperplasia / drug therapy*
  • Prostatic Hyperplasia / etiology
  • Prostatic Hyperplasia / pathology
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY

Substances

  • Antihypertensive Agents
  • Malondialdehyde
  • Losartan