カルシウム拮抗剤(Verapamil)の膀胱排尿筋収縮抑制作用臨床応用の可能性

Abstract

1)細胞膜のCa2+ channelに作用し, 細胞外カルシウムの細胞内への流入を選択的に阻害するカルシウム拮抗剤(verapamil)を用い, その家兎膀胱排尿筋収縮性に対する作用を, in vitroおよびin vovoにて検討した.2)排尿筋切片を用いたin vitro実験では, 筋切片の等長性収縮に対するverapamilの作用を検討した.acetylcholine (10-8～10-2 M), prostaglandin E2, F2-alpha (3×10-8～3×10-5 M)および電気刺激により惹起された筋切片収縮は, verapamil前処置により, dose-dependentに有意に抑制された.3)全膀胱標本を用いたin vitro実験では, 標本の等長張力変化を測定し, verapamil膀胱内注入の排尿筋収縮に対する作用を検討した.標本の自発収縮, acetylcholine (10-6 M)により惹起される収縮は, 7.5 mg verapamil注入後, time-dependentに有意に抑制され, 注入後90分には注入前の10%および38%にそれぞれ抑制された.この抑制作用は, verapamilを膀胱内より除去した後も2時間以上持続した.4) in vivo実験では, 両側骨盤神経の電気刺激による膀胱内圧の変化および全身血圧を測定, 記録し, verapamil膀胱内注入前後の変化を比較した.10 mg verapamil注入60分後, 骨盤神経刺激により惹起される膀胱内圧の上昇は注入前の18%に有意に抑制されたが, 他方全身血圧には有意な変化を認めなかった.5) Verapamil膀胱内注入は, 心血管系に有意な変化をおよぼすこと無く膀胱の収縮性を抑制し得ることが示唆された

Effects of a Ca2+ entry blocker (verapamil) on the contractility of the bladder detrusor muscle of rabbits were investigated in vitro and in vivo. In experiments using smooth muscle strips from the bladder detrusor, isometric tension changes of the strips following drug addition were recorded. The contractions of the strips induced by acetylcholine (10(-8)-10(-2)M), prostaglandin E2, F2-alpha (3 X 10(-8)-3 X 10(-5)M) or electric stimulation were significantly inhibited dose-dependently by pretreatment of the strips with verapamil (10(-7), 10(-6)M). In in vitro experiments using whole bladder preparations, the spontaneous contractile activity and the contraction induced by acetylcholine (10(-6)M) were monitored. Both activities were inhibited in a time-dependent manner after the intravesical instillation of 7.5 mg verapamil. The amplitude of the spontaneous contraction and responses to acetylcholine, 90 minutes after the instillation, were reduced to 10% and 38% of the control levels (before the instillation), respectively. The detrusor contractility was still inhibited 2 hours after the removal of verapamil from the bladder. During in vivo experiments, changes in intravesical pressure and systemic arterial pressure were monitored. Sixty minutes after the intravesical instillation of 10 mg verapamil, the rise of the intravesical pressure following the pelvic nerve stimulation was inhibited to 18% of the control level, whereas the systemic arterial pressure was not affected. Verapamil is suggested to have potent inhibitory effects on the detrusor muscle contraction, and the intravesical instillation of verapamil to inhibit detrusor contractility without affecting the cardiovascular status.