Inducible and neuronal nitric oxide synthase involvement in lipopolysaccharide-induced sphincteric dysfunction.
We examined the effect of endotoxin lipopolysaccharide (LPS) on the basal tone and on the effects of different stimuli and agonists and transcriptional and translational expression of nitric oxide (NO) synthase (NOS) isozymes in the lower esophageal sphincter (LES), pyloric sphincter (PS), and internal anal sphincter (IAS). NO release was also examined before and after LPS. LPS caused a dose-dependent fall in the basal tone and augmentation of the relaxation caused by nonadrenergic, noncholinergic (NANC) nerve stimulation in the LES and IAS. In the PS, LPS had no significant effect on the basal tone and caused an attenuation of the NANC relaxation and an augmentation of the contractile response of muscarinic agonist. Interestingly, the smooth muscle relaxation by atrial natriuretic factor was suppressed in the LES and IAS but not in the PS. These changes in the sphincteric function following LPS may be associated with increase in the inducible NOS (iNOS) expression since they were blocked by iNOS inhibitor L-canavanine. Augmentation of NANC relaxation in the LES and IAS smooth muscle by LPS may be due to the increased activity of neuronal NOS and NO production.
Fan
Y P
YP
Division of Gastroenterology and Hepatology, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Chakder
S
S
Gao
F
F
Rattan
S
S
D001003:Anal Canal / Q000201:enzymology / Q000294:innervation / Q000503:physiopathology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D018723:Bethanechol / Q000494:pharmacology; D004558:Electric Stimulation; D017615:Enteric Nervous System / Q000187:drug effects / Q000502:physiology; D004935:Esophageal Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D004943:Esophagogastric Junction / Q000201:enzymology* / Q000294:innervation / Q000503:physiopathology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000201:enzymology / Q000294:innervation / Q000503:physiopathology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D009893:Opossums; D010277:Parasympathomimetics / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011708:Pylorus; D013566:Sympathomimetics / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D008070:Lipopolysaccharides; D010277:Parasympathomimetics; D013566:Sympathomimetics; D014665:Vasodilator Agents; D018723:Bethanechol; D009599:Nitroprusside; D010656:Phenylephrine; D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin; D009320:Atrial Natriuretic Factor; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D007545:Isoproterenol; D009638:Norepinephrine