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他达拉非单次治疗对膀胱过度扩张/排空和腹主动脉夹闭/释放大鼠模型下尿路组织血流的影响。

Effect of a single treatment with tadalafil on blood flow in lower urinary tract tissues in rat models of bladder overdistension/emptying and abdominal aorta clamping/release.

机构信息

Research Laboratories, Nippon Shinyaku Co., Ltd., 14, Nishinosho-monguchi-cho, Kisshoin, Minami-ku, Kyoto 601-8550, Japan.

Research Laboratories, Nippon Shinyaku Co., Ltd., 14, Nishinosho-monguchi-cho, Kisshoin, Minami-ku, Kyoto 601-8550, Japan.

出版信息

Eur J Pharmacol. 2015 May 5;754:92-7. doi: 10.1016/j.ejphar.2015.01.050. Epub 2015 Feb 17.

Abstract

Impaired blood flow in lower urinary tract (LUT) tissues is a pathophysiological cause of LUT symptoms. We investigated the effects of the phosphodiesterase 5 (PDE5) inhibitor tadalafil on the sustained decrease in bladder blood flow (BBF) and time-dependent changes in BBF and prostate blood flow (PBF) resulting from ischemia/reperfusion in two rat models. In a rat model of bladder overdistension/emptying (O/E), the bladder was overdistended by saline infusion and emptied after 2h. Tadalafil was administered intraduodenally immediately after emptying. In a rat model of clamping/release (C/R), the abdominal aorta was clamped for 2h after a single oral dose of tadalafil and then the clamp was released. BBF in O/E and C/R rats and PBF in C/R rats were measured by laser Doppler flow imaging. BBF decreased on overdistension and partially recovered after emptying. A progressive decrease in BBF was observed after O/E, and this was prevented by tadalafil treatment. Both BBF and PBF decreased during clamping of the abdominal aorta and partially recovered after clamp removal. Oral pretreatment with tadalafil partially or completely prevented the decreases in BBF and PBF not only after clamp removal but also during clamping. PDE5 mRNA was highly expressed in the bladder and the supporting vasculature. Tadalafil inhibited the O/E-induced decrease in BBF and the C/R-induced time-dependent decreases in BBF and PBF. PDE5 inhibition by tadalafil may improve both BBF and PBF.

摘要

下尿路 (LUT) 组织的血液流动受损是 LUT 症状的病理生理原因。我们研究了磷酸二酯酶 5 (PDE5) 抑制剂他达拉非对两种大鼠模型中缺血/再灌注引起的膀胱血流 (BBF) 持续减少和 BBF 及前列腺血流 (PBF) 的时变变化的影响。在膀胱过度扩张/排空 (O/E) 的大鼠模型中,通过盐水输注使膀胱过度扩张,2 小时后排空。排空后立即经十二指肠给予他达拉非。在夹闭/释放 (C/R) 的大鼠模型中,单次口服他达拉非后夹闭腹主动脉 2 小时,然后释放夹闭。通过激光多普勒血流成像测量 O/E 和 C/R 大鼠的 BBF 和 C/R 大鼠的 PBF。膀胱过度扩张时 BBF 减少,排空后部分恢复。O/E 后观察到 BBF 逐渐减少,他达拉非治疗可预防这种减少。夹闭腹主动脉时 BBF 和 PBF 均减少,夹闭解除后部分恢复。口服他达拉非预处理不仅在夹闭解除后,而且在夹闭过程中部分或完全预防了 BBF 和 PBF 的减少。PDE5 mRNA 在膀胱和支持血管中高度表达。他达拉非抑制 O/E 诱导的 BBF 减少和 C/R 诱导的 BBF 和 PBF 的时变减少。PDE5 抑制可能改善 BBF 和 PBF。

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