Journal of Smooth Muscle Research
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Volume 47 , Issue 6
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Original
  • Katsuhiko Iwakiri, Noriyuki Kawami, Hirohito Sano, Yuriko Tanaka, Mari ...
    Type: Original
    Volume 47 (2011) Issue 6 Pages 157-166
    Released: February 29, 2012
    JOURNALS FREE ACCESS
    Background: A study in Japan has found that nizatidine (NIZ) is more effective than other histamine H2 receptor agonists (H2RAs) in treating reflux esophagitis (RE), although the NIZ group included a greater number of patients with severe RE. As there was no difference in the level of acid suppression among H2RAs, it is possible that NIZ has other effects on esophageal acid exposure (EAE) besides acid suppression. In this study, the effect of NIZ on transient lower esophageal sphincter relaxations (TLESRs) and acid reflux was evaluated in healthy subjects. Methods: In 10 healthy subjects, while in a sitting position, esophageal motility and a pH study were measured for 3 hours after a meal on 2 separate days at least 2 weeks apart. Participants received an oral dose of 150 mg of NIZ, 60 min before the meal on one day and a placebo on the other. Both studies were preceded by a week of treatment with either NIZ (150 mg, bid) or a placebo and the order of treatment was randomized. Results: Basal LES pressure in the NIZ group (14.1 mmHg, median) was significantly greater than that of the placebo group (8.5 mmHg). The rate of TLESRs in the NIZ group (22.0/3 h) for the postprandial 3-hour period was significantly less than that of the placebo group (16.5/3 h) and the rate of acid reflux during TLESRs (24.7%) and the EAE (0.2%) in the NIZ group for the postprandial 3-hour period was also significantly less than that of the placebo group (74.4% and 2.8%, respectively). Conclusion: NIZ significantly reduces acid reflux by inhibiting both the rate of TLESRs and acid reflux during TLESRs.
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  • Hiroyuki Fujimoto, Yuhsuke Shigemasa, Hikaru Suzuki
    Type: Original
    Volume 47 (2011) Issue 6 Pages 167-182
    Released: February 29, 2012
    JOURNALS FREE ACCESS
    Mechanical responses of smooth muscle elicited by application of CO2-gas bubbled physiological salt solution (CO2-gas solution) were investigated in isolated stomach antrum and colon preparations of the guinea-pig. Circular smooth muscle preparations of both colon and stomach were spontaneously active with periodic generation of phasic contractions. In colonic preparations, the CO2-gas solution produced a biphasic response, with an initial small transient contraction followed by a sustained inhibition of phasic contractions. Removal of the CO2-gas solution allowed a slow recovery of the spontaneous contractions over a period of about 40 min. The recovery developed with a similar time course irrespective of the length of time exposed to CO2-gas solution. The inhibitory responses elicited by CO2-gas solution were not modulated by atropine, Nω-nitro-L-arginine or neostigmine. Atropine-sensitive excitatory responses of smooth muscle elicited by transmural nerve stimulation or exogenously applied acetylcholine were attenuated or abolished in the presence of CO2-gas solution. In stomach preparations, the CO2-gas solution elicited a tri-phasic response, with an initial transient relaxation followed by a transient contraction and then a sustained inhibition of the rhythmic contractions. The peak amplitude of the transient contraction was about 2.5 times larger than the spontaneous phasic contractions. The pH of the CO2-gas solution was reduced to about 6. Application of pH 6 solution again produced a tri-phasic response, as was the case for the CO2-gas solution, however the amplitude of the transient contraction was only about 0.4 times that of the spontaneous contractions. The re-appearance of the abolished phasic contraction was quicker with the pH 6 solution (about 1.8 min) than it was for the CO2-gas solution (about 6 min). The inhibitory responses elicited by the CO2-gas solution could be simulated only partly by the acidified solution, and a possible involvement of additional factors in the inhibition elicited by CO2-gas solution was considered.
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