title: Effect of nifedipine on anorectal sensorimotor functions in health and fecal incontinence.
abstract: The mechanisms of increased rectal stiffness in women with fecal incontinence (FI) and rectal urgency are not understood. Our hypothesis was that distention-induced activation of mechanosensitive L-type calcium channels in smooth muscle contributes to increased rectal stiffness in FI. Anal pressures, rectal distensibility (compliance, capacity, and contractile response to sinusoidal oscillation), and rectal sensation were assessed before and after oral nifedipine (30 + 10 mg) or placebo in 16 women with FI and 16 asymptomatic women. At baseline, FI patients had a lower anal pressure increment during squeeze (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 during sinusoidal oscillation (health, 13.7 ± 3.2: FI, 21.7 ± 1.4, mean ± SE, P = 0.02) than the healthy women, which suggests an exaggerated rectal contractile response to distention. Nifedipine decreased mean BP, increased heart rate (P = 0.01 vs. placebo), and reduced anal resting pressure (P ≤ 0.01) but did not significantly modify rectal distensibility in health or FI. Plasma nifedipine concentrations (health, 103 ± 21 ng/ml: FI, 162 ± 34 ng/ml) were correlated with increased rectal compliance (r = 0.6, P = 0.02) in all study participants and, in healthy subjects, with decreased rectal pressures during sinusoidal oscillation (r = 0.86, P = 0.01), indicative of reduced stiffness. No consistent effects on rectal perception were observed. These observations confirm that FI is associated with anal weakness and increased rectal stiffness. At therapeutic plasma concentrations, nifedipine reduced anal resting pressure but did not improve rectal distensibility in FI, outcomes that argue against a predominant contribution of myogenic L-type calcium channels to reduced rectal distensibility in FI.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA. bharucha.adil@mayo.edu
authors.forename: Adil E
authors.initials: AE
authors.lastname: Bharucha
authors.forename: Jessica
authors.initials: J
authors.lastname: Edge
authors.forename: Alan R
authors.initials: AR
authors.lastname: Zinsmeister
mesh_terms: D000328:Adult; D001003:Anal Canal / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D005242:Fecal Incontinence / Q000188:drug therapy* / Q000503:physiopathology*; D056228:Feedback, Sensory / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D009543:Nifedipine / Q000008:administration & dosage*; D012007:Rectum / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D009543:Nifedipine