Inhibition of Contractility of Isolated Caprine Detrusor by the Calcium Channel Blocker Cilnidipine and Reversal by Calcium Channel Openers

IF 1.6 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Current Therapeutic Research-clinical and Experimental Pub Date : 2023-01-01 DOI:10.1016/j.curtheres.2023.100717

Steffi A. Maria MD, Aniket Kumar PhD, Premila M. Wilfred MD, Margaret Shanthi MD, Jacob Peedicayil MD

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引用次数: 0

Abstract

Background

Cilnidipine is a fourth-generation calcium channel blocker that is clinically used to treat hypertension. It is a dihydropyridine that blocks L- and N-type calcium channels. The inhibitory effect of cilnidipine on isolated detrusor muscle contractility has not been studied. This study investigated the inhibitory effect of cilnidipine on isolated caprine (goat) detrusor muscle contractility and the reversal of the inhibition by calcium channel openers.

Methods

Fourteen caprine detrusor strips were made to contract using 80 mM potassium chloride before and after addition of three concentrations (20, 40, and 60 µM) of cilnidipine. Two reversal agents, the L-type calcium channel opener FPL64716, and the N-type calcium channel opener GV-58, were investigated for their ability to reverse the inhibitory effect of 40 µΜ cilnidipine on potassium chloride-induced detrusor contractility.

Results

Cilnidipine caused a dose-dependent and statistically significant inhibition of detrusor contractility at all concentrations of cilnidipine used (20, 40, and 60 µΜ). The inhibitory effect of 40 µM cilnidipine on detrusor contractility was significantly reversed by the addition of FPL64716 and GV-58.

Conclusions

Cilnidipine inhibits the contractility of the isolated detrusor by blocking L- and N-type calcium channels. Cilnidipine could be evaluated for treating clinical conditions requiring relaxation of the detrusor such as overactive bladder.

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钙通道阻断剂西尼地平对分离的Caprine Detrusor收缩的抑制作用和钙通道开放剂的逆转作用。

背景：西尼地平是临床上用于治疗高血压的第四代钙通道阻滞剂。它是一种阻断L型和N型钙通道的二氢吡啶。西尼地平对离体逼尿肌收缩力的抑制作用尚未得到研究。本研究研究了西尼地平对山羊逼尿肌收缩力的抑制作用以及钙通道开放剂对其抑制作用的逆转作用。方法：在添加三种浓度（20、40和60µM）的西尼地平之前和之后，使用80mM氯化钾使14条山羊逼尿肌条收缩。研究了两种拮抗剂，L型钙通道阻滞剂FPL64716和N型钙通道调节剂GV-58，逆转40µΜ西尼地平对氯化钾诱导的逼尿肌收缩力的抑制作用。结果：在所有浓度的西尼地平（20、40和60µΜ）下，西尼地平对逼尿肌收缩力产生剂量依赖性且具有统计学意义的抑制作用。40µM西尼地平对逼尿肌收缩力的抑制作用通过添加FPL64716和GV-58显著逆转。结论：西尼地平通过阻断L型和N型钙通道抑制分离的逼尿肌的收缩力。西尼地平可用于治疗需要放松逼尿肌的临床病症，如膀胱过度活动。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Therapeutic Research-clinical and Experimental 医学-药学

CiteScore

3.50

自引率

0.00%

发文量

审稿时长

3 months

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