Abstract
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. 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 x 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. Erythromycin 5 x 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 x 10(-4) M was added together with nifedipine 10(-8) M, the response to carbachol was inhibited by a further 25% (P < 0.005). Erythromycin inhibits rat detrusor muscle contraction through the inhibition of calcium influx and the modulation of intracellular calcium movement.
Highlights
Estimates for the prevalence of overactive bladder (OAB) range between 3 and 43% depending on the study method used and the age of the patient [Milsom et al 2000]
It was concluded that the mode of action of erythromycin on rat detrusor smooth muscle contraction was due to a direct effect on the detrusor muscle
Effect of ethanol on electrical field stimulation (EFS)-evoked responses Ethanol 0.25% had no effect on the maximum contractile response of rat detrusor muscle to EFS (Fig 1)
Summary
Estimates for the prevalence of overactive bladder (OAB) range between 3 and 43% depending on the study method used and the age of the patient [Milsom et al 2000]. Nissan et al (1999) demonstrated that erythromycin inhibited the contractile response of rat detrusor muscle to carbachol and electrical field stimulation (EFS) but not to bradykinin, phenylephrine or substance P. This inhibitory effect of erythromycin on EFS-evoked responses was not altered in the presence of tetrodotoxin (TTX), which blocks presynaptic activation and neurotransmitter release. The present study was conducted to further investigate the mechanisms of action of erythromycin on the contractile response of isolated rat detrusor muscle and to investigate the hypothesis that an effect on calcium signalling is responsible
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