Effect of nifedipine on anorectal sensorimotor functions in healthand fecal incontinence

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.