Direct inhibition of rat detrusor muscle contraction by erythromycin

Purpose Detrusor instability is a common problem in the elderly, which is usually treated with anti-cholinergic medication. This study investigates the effect of erythromycin on rat detrusor muscle contractile response to characterise its potential as an alternative inhibitor of bladder muscle contraction. Materials and Methods Strips of rat detrusor muscle were suspended in a perfusion organ bath. The contractile response to direct muscle stimulation, electrical field stimulation (EFS, 0.5–60 Hz), carbachol (10−5 M), and potassium (10–80 × 10−3 M) were determined before and after the addition of erythromycin (10−4–10−3 M). The contractile response to carbachol (10−5 M) in the presence of nifedipine (10−8 or 10−6 M) or in calcium-free Kreb's solution was also determined in the absence and presence of erythromycin. Results Erythromycin 5 × 10−4 M inhibited the maximum contractile response to EFS, carbachol, and potassium by 38% (P < 0.01), 62% (P < 0.001), and 17% (P < 0.05), respectively, but did not significantly reduce the response to direct muscle stimulation. The atropine-resistant component of EFS-evoked contraction was inhibited by 19.5% (P < 0.01) in the presence of erythromycin. In calcium-free Krebs solution, the maximum contractile response to carbachol was reduced by 42% of control (P < 0.0001) and nifedipine 10−8 M had no additional effect. When erythromycin 5 × 10−4 M was added together with nifedipine 10−8 M, the response to carbachol was inhibited by a further 25% (P < 0.005). Conclusions Erythromycin inhibits rat detrusor muscle contraction through the inhibition of calcium influx and the modulation of intracellular calcium movement.