Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Japan.
Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Japan.
Eur J Pharmacol. 2020 Sep 5;882:173313. doi: 10.1016/j.ejphar.2020.173313. Epub 2020 Jun 27.
We investigated the effects of the phosphodiesterase type 5 inhibitor, tadalafil on prostatic hyperplasia in a hypertensive rat model. Twelve-week-old male spontaneously hypertensive rats (SHRs) were orally treated with tadalafil (2 or 10 mg/kg/day) or vehicle for six weeks. Wistar Kyoto (WKY) rats treated with vehicle were used as controls. The effect of tadalafil was evaluated by measuring prostate weight, blood pressure, and prostatic blood flow. The presence of malondialdehyde (MDA), interleukin-6 (IL-6), transforming growth factor-beta1 (TGF-β1), and basic fibroblast growth factor (bFGF) in the ventral prostate were examined. Hematoxylin and eosin staining was performed to assess the morphological change. The prostatic contractility was evaluated by an organ bath experiment. The vehicle-treated SHRs demonstrated a significantly higher prostate weight, prostate weight/body weight ratio (PBR), blood pressure, and tissue levels of MDA, IL-6, TGF-β1, and bFGF, and lower prostatic blood flow compared to the vehicle-treated WKY rats. Moreover, the SHRs showed glandular morphological abnormalities in the ventral prostate compared to the WKY rats. There was no significant difference in potassium chloride or noradrenaline-induced prostatic contractility between the WKY rats and the SHRs. Treatment with tadalafil decreased prostate weight and PBR in a dose-dependent manner, and improved prostatic blood flow and tissue levels of MDA, IL-6, TGF-β1, and bFGF in SHRs, without affecting the blood pressure. Furthermore, tadalafil ameliorated the glandular morphological abnormalities in the SHR ventral prostate. In conclusion, tadalafil could suppress the prostatic hyperplasia via recovery of reduction in prostatic blood flow in SHRs.
我们研究了磷酸二酯酶 5 抑制剂他达拉非对高血压大鼠前列腺增生的影响。12 周龄雄性自发性高血压大鼠（SHR）口服他达拉非（2 或 10mg/kg/天）或载体 6 周。用载体处理的 Wistar Kyoto（WKY）大鼠用作对照。通过测量前列腺重量、血压和前列腺血流量来评估他达拉非的作用。检查了腹侧前列腺中丙二醛（MDA）、白细胞介素-6（IL-6）、转化生长因子-β1（TGF-β1）和碱性成纤维细胞生长因子（bFGF）的存在。进行苏木精和伊红染色以评估形态变化。通过器官浴实验评估前列腺的收缩性。与载体处理的 WKY 大鼠相比，载体处理的 SHR 显示出明显更高的前列腺重量、前列腺重量/体重比（PBR）、血压以及 MDA、IL-6、TGF-β1 和 bFGF 的组织水平，并且前列腺血流量较低。此外，与 WKY 大鼠相比，SHR 在腹侧前列腺中显示出腺体形态异常。WKY 大鼠和 SHR 之间氯化钾或去甲肾上腺素诱导的前列腺收缩性没有差异。他达拉非以剂量依赖性方式降低前列腺重量和 PBR，改善 SHR 前列腺血流量和 MDA、IL-6、TGF-β1 和 bFGF 的组织水平，而不影响血压。此外，他达拉非改善了 SHR 腹侧前列腺的腺体形态异常。总之，他达拉非可通过恢复 SHR 前列腺血流量减少来抑制前列腺增生。
