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Prostate. 2015 Nov;75(15):1774-82. doi: 10.1002/pros.23063. Epub 2015 Aug 19.

Protective effect of hydroxyfasudil, a Rho kinase inhibitor, on ventral prostatic hyperplasia in the spontaneously hypertensive rat.

Author information

1
Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Japan.
2
Department of Urology, Yale University School of Medicine, New Haven, Connecticut.
3
Department of Surgery, Division of Urology, Tottori University School of Medicine, Yonago, Japan.

Abstract

BACKGROUND:

Rho kinase (ROCK) pathway is associated with various cellular functions, such as smooth muscle contraction, inflammatory response, and cell proliferation. The spontaneously hypertensive rat (SHR) is commonly used genetically hypertensive rat model which develops hyperplastic morphological abnormalities in the ventral prostate. We investigated whether administration of hydroxyfasudil, a ROCK inhibitor, could reduce the levels of growth factors, inflammatory markers, and morphological abnormalities in the ventral prostate of the SHR.

METHODS:

Twelve-week-old SHRs were treated with hydroxyfasudil (1 mg/kg/day, i.p.) or vehicle once daily for another 6 weeks. Wistar Kyoto (WKY) rats treated with vehicle were used as normotensive controls. At 18 weeks of age, blood pressure and heart rate were measured by the tail cuff method. Then the rats were sacrificed, and the ventral prostates were removed. The levels of ROCK activity, growth factors (TGF-β1 and bFGF), a smooth muscle differentiation marker (α-SMA) and an inflammatory cytokine (IL-6) in the ventral prostate were measured by ELISA and western blot. A histological evaluation in each group was also performed.

RESULTS:

There were significant increases in blood pressure, prostate weight, prostate body weight ratio, and tissue levels of ROCK activity, TGF-β1, bFGF, α-SMA, and IL-6 in the SHR compared to the WKY rat. Histological examination of the ventral prostate showed morphological abnormalities such as a higher degree of proliferation in the glandular epithelial and stromal area in the SHR compared to the WKY rat. Treatment with hydroxyfasudil reduced the elevated ROCK activity, TGF-β1, bFGF, α-SMA, and IL-6 found in the ventral prostate of the SHR. Moreover, treatment with hydroxyfasudil decreased the morphological abnormalies in the SHR ventral prostate.

CONCLUSIONS:

Treatment with hydroxyfasudil decreased the growth factors, an inflammatory cytokine, and morphological abnormalies in the SHR ventral prostate. These results suggest that chronic treatment with hydroxyfasudil may inhibit the progression of prostatic hyperplasia in the SHR.

KEYWORDS:

growth factor; hydroxyfasudil; prostate; spontaneously hypertensive rat

PMID:
26286428
DOI:
10.1002/pros.23063
[Indexed for MEDLINE]

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