Hsu Chun-Kai, Chang Hsi-Hsien, Yang Stephen Shei-Dei
Division of Urology, Department of Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan.
School of Medicine, Tzu Chi University, Hualien, Taiwan.
Tzu Chi Med J. 2019 Feb 18;32(1):26-29. doi: 10.4103/tcmj.tcmj_178_18. eCollection 2020 Jan-Mar.
We have demonstrated that phenylephrine (PE) activates the capsaicin-sensitive nerves, and then activates capsaicin-sensitive nerves to release an unknown substance that facilitates the release of norepinephrine (NE) from adrenergic nerves. Subsequently, NE stimulates β-ARs in the detrusor muscle in mice, leading to neurogenic relaxation of the urinary bladder (UB).
We examined if there existed sensory-motor dysfunction in UB of aging mice. To investigate the change of PE-induced detrusor relaxation in aging male-C57BL/6 mice (12- vs. 24-month-old mice), UB strips from mice were isolated, cut into strips, and mounted in the organ bath.
The UB strip contractility responding to various agents was estimated using tissue bath wire myography. Acetylcholine (ACh) and KCl-induced UB strips contraction was not significantly different between 24- and 12-month mice. NE-induced UB strips relaxation was significantly lower in 24-month than 12-month mice. Denuded bladder strips showed similar decreased relaxation response to NE. This NE-induced relaxation was inhibited by silodosin and lidocaine. PE did not induce contraction in UB strips of aging mice. In contrast, PE-induced relaxation was weaker in 24-month than 12-month mice.
Our results suggested that the PE-induced relaxation was age related. Aging seemed to lead the sensory-motor dysfunction. More animal and human studies are required to prove this concept and its clinical usefulness in the future.
我们已经证明，去氧肾上腺素（PE）可激活辣椒素敏感神经，进而激活辣椒素敏感神经释放一种未知物质，该物质可促进去甲肾上腺素能神经释放去甲肾上腺素（NE）。随后，NE刺激小鼠逼尿肌中的β-肾上腺素能受体（β-ARs），导致膀胱（UB）神经源性舒张。
我们研究了衰老小鼠的膀胱是否存在感觉运动功能障碍。为了研究衰老雄性C57BL/6小鼠（12月龄与24月龄小鼠）中PE诱导的逼尿肌舒张的变化，从小鼠分离出膀胱条，切成条带，并安装在器官浴槽中。
使用组织浴线肌动描记法评估膀胱条对各种药物的收缩反应。24月龄和12月龄小鼠中，乙酰胆碱（ACh）和氯化钾诱导的膀胱条收缩无显著差异。24月龄小鼠中NE诱导的膀胱条舒张显著低于12月龄小鼠。去上皮膀胱条对NE的舒张反应也有类似程度的降低。这种NE诱导的舒张被西洛多辛和利多卡因抑制。PE未诱导衰老小鼠膀胱条收缩。相反，24月龄小鼠中PE诱导的舒张比12月龄小鼠弱。
我们的结果表明，PE诱导的舒张与年龄有关。衰老似乎导致感觉运动功能障碍。未来需要更多的动物和人体研究来证实这一概念及其临床实用性。
