Effects of verapamil and sodium nitroprusside on acetylcholine-induced contraction of the rabbit detrusor muscle

Summary 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 contration, 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 dosedependent 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 in tracellular Ca²⁺ fractions will partly participate in the acetylcholine-induced contration and possibly in its maintenance.