Effects of nifedipine on anorectal smooth muscle in vitro

INTRODUCTION: Glyceryl trinitrate reduces anal resting pressure and aids th e healing of anal fissures. However, some patients develop tachyphylaxis an d the fissure fails to heal, suggesting that other agents are needed. This study assesses the effects of nifedipine (a calcium channel antagonist) in modulating resting tone and agonist-induced contractions in human internal anal sphincter (LAS) and rectal circular muscle. METHODS: Smooth muscle str ips from the IAS and rectal circular muscle from ten patients undergoing su rgical resection were mounted for isometric tension recording in a superfus ion organ bath. The effects of noradrenaline and carbachol were assessed in the presence of various perfusates, RESULTS: LAS strips developed tone and spontaneous activity. Noradrenaline produced dose-dependent contractions. In calcium-free Krebs solution, tone and activity were abolished and no con tractions were elicited in response to noradrenaline. Nifedipine also aboli shed tone and spontaneous activity, but contractions to noradrenaline were only slightly attenuated. in contrast, rectal smooth muscle strips develope d spontaneous activity but no resting tone and contracted in response to ca rbachol. In calcium-free Krebs solution, the spontaneous activity and carba chol contractions were abolished. Addition of nifedipine to the perfusate a bolished spontaneous activity and greatly reduced contractions. DISCUSSION: These data suggest that spontaneous activity and resting tone are dependen t on extracellular calcium and flux across the cells. Agonist-induced contr action in the LAS is attributable mainly to the release of calcium from int racellular stores, whereas rectal circular smooth muscle depends principall y on extracellular calcium entering the cell for contraction. The attenuati on of contractions in both tissues and the abolition of resting tone in the IAS suggest that nifedipine mall be useful in the management of patients w ith anorectal disorders.