Effect of nifedipine on anorectal sensorimotor functions in healthand fecal incontinence

Adil E. Bharucha, Jessica Edge, Alan R. Zinsmeister

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The mechanisms of increased rectal stiffness in women with fecal incontinence(FI) and rectal urgency are not understood. Our hypothesiswas that distention-induced activation of mechanosensitive L-typecalcium channels in smooth muscle contributes to increased rectalstiffness in FI. Anal pressures, rectal distensibility (compliance, capacity,and contractile response to sinusoidal oscillation), and rectalsensation were assessed before and after oral nifedipine (30 + 10 mg)or placebo in 16 women with FI and 16 asymptomatic women. Atbaseline, FI patients had a lower anal pressure increment duringsqueeze (health, 66.9 ± 7.6: FI, 28.6 ± 5.9, mean ± SE, P ≤ 0.01),lower rectal capacity (P = 0.052), and higher rectal pressures duringsinusoidal oscillation (health, 13.7 ± 3.2: FI, 21.7 ± 1.4, mean ± SE,P = 0.02) than the healthy women, which suggests an exaggeratedrectal contractile response to distention. Nifedipine decreased meanBP, increased heart rate (P = 0.01 vs. placebo), and reduced analresting pressure (P ≤ 0.01) but did not significantly modify rectaldistensibility in health or FI. Plasma nifedipine concentrations (health,103 ± 21 ng/ml: FI, 162 ± 34 ng/ml) were correlated with increasedrectal compliance (r = 0.6, P = 0.02) in all study participants and, inhealthy subjects, with decreased rectal pressures during sinusoidaloscillation (r = 0.86, P = 0.01), indicative of reduced stiffness. Noconsistent effects on rectal perception were observed. These observationsconfirm that FI is associated with anal weakness and increasedrectal stiffness. At therapeutic plasma concentrations, nifedipine reducedanal resting pressure but did not improve rectal distensibility inFI, outcomes that argue against a predominant contribution of myogenicL-type calcium channels to reduced rectal distensibility in FI.

Original languageEnglish (US)
Pages (from-to)1522-1547
Number of pages26
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume301
Issue number1
DOIs
StatePublished - Jul 2011

Keywords

  • Calcium channel blockers
  • Pressure
  • Rectal capacity
  • Rectal compliance
  • Sensation

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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