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The Effect of Intravesical Capsaicin on Detrusor Contractility-a Study of the Concentration and Duration in Rat Urinary Bladders

紅辣椒素對逼尿肌收縮力之影響-大白鼠膀胱內灌注於不同濃度及時間之研究

摘要


為了瞭解膀胱內灌注紅辣椒素時濃度與時間對於排尿反射與逼尿肌收縮力之影響,我們使用正常成鼠進行(1)活體膀胱壓,(2)離體全膀胱以及(3)離體肌肉條之收縮研究。 在活體膀胱壓研究中,我們使用1,10,100,1000 µ M之紅辣椒素灌注入urethane麻醉之大白鼠膀胱,控制組則使用含有10% ethanol,10% Tween 80以及80%生理鹽水之媒介物。第二組實驗中,我們使用媒介物(控制組)及1000µ M紅辣椒素灌注膀胱,並存留1,2,4小時,比較每一組之膀胱活動力。在活動膀胱壓實驗後,取下膀胱,懸吊於organ bath中,進行離體全膀胱收縮力研究。我們使用電刺激,bethanechol 藥物制激以及KC1刺激並記錄膀胱內壓之改變。第三步驟我們切開4個控制組膀胱以及每一組二個膀胱以進行離體肌肉條之收縮力研究,並比較不同條件處理後之逼尿肌收縮力。 本研究結果顯示,膀胱內灌注紅辣淑素在100 µ M濃度以上可以抑制排尿反射,較高的濃度可以激發濃度相關之膀胱活動力。然而在離體研究中,逼尿肌收縮力並沒有太大的受到影響。較長時間的浸泡紅辣椒素在逼尿肌收縮力上也沒有太大的差異性。 我們推測,在表皮下的neurokinin受器會被膀胱內灌注之紅辣椒素所激發,經由感覺神經未稍釋放出之tachykinins可以調解排尿反射。只有在高於100 µ M濃度,紅辣椒素才以抑制排尿反射,但是較長時間的暴露並無法使神經末稍繼續釋放tachykinins,對逼尿肌收縮力也沒有太大的影響。

並列摘要


In order to clarify the influence of concentration and duration of intravesical capsaicin exposure on the micturition reflex and detrusor contractility, normal adult rats were used in in vivo cystometry, in vitro whole bladder study and in vitro muscle strip study. In in vivo cystometry, Capsaicin at the concentrations of 1, 10, 100 and 1000 µ M were infused into urethane-anesthetized rat bladders. Vehicle containing 10% Tween 80 and 80% normal saline was used for control studies. In the secoud study, vehicle and 1000 µ M capsaicin were infused into the bladders and were retained for 1, 2 and 4 hours. The bladder activities after each type of infusion were recorded and compared. Then the bladders were resected and suspended in the organ baths. In vitro whole bladder contractility was performed by recording of the intravesical pressure under electrical, bethanechol and KCl simulations. Some bladders were harvested after in vivo cystometry and isolated muscle strip contractility study were undertaken under the same stimulations. The results of this study showed that intravesical capsaicin administration could inhibit micturition reflex at the concentrations of at least 100 µ M. A higher concentration of capsaicin administered intravesically could activate concentration- dependent this concentration. A longer duration of intravesical exposure to 1000 µ M capsaicin did not show a better inhibitory effect on detrusor contractility than vehicle pretreated bladders. It is postulated that the neurokinin receptors in the urothelium can be activated by intravesical capsaicin administration. The tahykinins released from afferent nerve terminals can modulate the micturition reflex. However, only under a concentration of at least 100µ M capsaicin can inhibit the reflex through influencing the neurokinin receptors in the detrusor muscle or intramural ganglia. A longer duration of intravesical exposure up to 4 hours did not induce a larger amount of tachykinin releases, and hence had no effect on the detrusor contractility.

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