Effects of verapamil and sodium nitroprusside on acetylcholine-induced contraction of the rabbit detrusor muscle.
Effects of extracellular and intracellular Ca2+ on acetylcholine-induced contraction of the bladder detrusor muscle were studied in vitro, utilizing two types of Ca2+ antagonists of different mechanisms of action; verapamil and sodium nitroprusside (NP). Acetylcholine (10(-8) to 10(-2) M) caused dose-dependent contractions of the detrusor muscle strips. Pretreatment of the strips with verapamil (10(-7), 10(-6) M) significantly inhibited the acetylcholine-induced contraction in a dose-dependent manner, whereas NP (10(-7) to 10(-5) M) failed so suppress the contraction. The contraction of the strips once elicited by acetylcholine (10(-6) M) could be completely relaxed by verapamil (10(-5) M) addition, but only incompletely by NP (10(-5), 10(-4) M). In Ca2+-free solution containing 0.01 mM EGTA, replenishment of Ca2+ (2.5 mM) to the medium caused contractions of the strips. Addition of acetylcholine (10(-6) M) to the medium enhanced the Ca2+-induced contraction, which was significantly inhibited by pretreatment with verapamil (10(-6) M), but not affected by NP (10(-6) M). In Ca2+-free medium containing 0.1 mM EGTA, acetylcholine caused a slight degree of tension increase of the strips in a dose-dependent fashion, at higher concentrations exceeding 10(-6) M. These results suggest that the detrusor muscle contraction induced by acetylcholine is mostly dependent of extracellular Ca2+ influx both in its initiation and maintenance. It is also supposed, however, that intracellular Ca2+ fractions will partly participate in the acetylcholine-induced contraction and possibly in its maintenance.
Department of Urology, Nagoya University School of Medicine, Japan.
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Gotoh
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Kondo
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Hassouna
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Elhilali
D000109:Acetylcholine; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002413:Cations, Divalent; D004305:Dose-Response Relationship, Drug; D005292:Ferricyanides / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology*; D011817:Rabbits; D014700:Verapamil / Q000494:pharmacology*
D002413:Cations, Divalent; D005292:Ferricyanides; D009599:Nitroprusside; D014700:Verapamil; D000109:Acetylcholine; D002118:Calcium