[Mechanism of relaxation mediated by nitric oxide on human lower esophageal sphincter].
OBJECTIVE
To explore the mechanism of relaxation mediated by nitric oxide on the human lower esophageal sphincter (LES), and compare the difference in relaxation response between clasp fibers and sling fibers.


METHODS
32 LES specimens were obtained from 32 patients with high-positioned carcinoma of the mid-esophagus, 12 males and 16 females, aged 55.9 +/- 9.3, during operation. The clasp fibers and sling fibers were isolated and suspended in perfusion tough. Electric field stimulation (EFS) was applied to the clasp and sling fibers in vitro. Nitric oxide synthase (NOS) inhibitor L-NNA, NOS substrate L-arginine, neurotoxin tetrodotoxin (TTX), and atropine were added respectively to observe their effects on the clasp and sling fibers under EFS. Sodium nitroprusside was added on the two kinds of smooth muscle stripes to observe its influence as well.


RESULTS
EFS induced frequency-dependent relaxation to clasp fibers and some of sling fibers, which was inhibited by L-NNA in a concentration-dependent manner and was reversed by L-arginine partially. Maximal relaxation in clasp fibers and sling fibers was observed at 512 Hz and 16 Hz respectively. The higher amplitude relaxation was induced in the sling fibers at lower stimulus frequencies (< 32 Hz). Conversely, the same response was induced in the clasp fibers at higher stimulus frequencies (> 64 Hz). Meanwhile, off-contraction was induced by EFS in some sling fibers and clasp fibers. In some sling fibers, contraction was induced by EFS which was inhibited by atropine. Maximal contraction in these fibers was observed at 128 Hz. TTX abolished the effect of EFS on both clasp and sling fibers, which was considered neurogenic. Sodium nitroprusside elicited the similar response to EFS.


CONCLUSIONS
Relaxation of clasp and sling fibers is related to L-NNA, TTX, and sodium nitroprusside, and can be mediated by nitric oxide. Lower stimulus frequencies induce higher amplitude relaxation to sling fibers, and conversely, higher stimulus frequencies induce higher amplitude relaxation to clasp fibers. EFS induces contraction response in some sling fibers.
Wen
Shi-wang
SW
Department of Thoracic Surgery, Hebei Province Tumor Hospital, Shijiazhuang 050011, China.
Liu
Jun-feng
JF
Gao
Li-ping
LP
Tian
Zi-qiang
ZQ
Wang
Qi-zhang
QZ
Li
Bao-qing
BQ
D000368:Aged; D001120:Arginine / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D049630:Esophageal Sphincter, Lower / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D013779:Tetrodotoxin; D001285:Atropine; D001120:Arginine; D019001:Nitric Oxide Synthase