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Rheumatology Advance Access published online on November 20, 2009
Rheumatology, doi:10.1093/rheumatology/kep313
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© The Author(s) 2009. Published by Oxford University Press on behalf of The British Society for Rheumatology.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Inducible nitric oxide synthase increases secretion from inflamed salivary glands

Patricia N. Correia1, Guy H. Carpenter1, Katherine L. Paterson1 and Gordon B. Proctor1

1Salivary Research Unit, King's College London Dental Institute, Guy's and St Thomas' Hospitals, London, UK.

Correspondence to: Gordon B. Proctor, Salivary Research Unit, Floor 17, The Tower Wing, King's College London Dental Institute, Guy's and St Thomas’ Hospitals, Great Maze Pond, London SE1 9RT, UK. E-mail: gordon.proctor{at}kcl.ac.uk


  Abstract

Objective. Salivary gland secretion is dependent on cholinergic stimulation via autonomic nerves and calcium signalling in acinar cells. Secretory dysfunction associated with SS may be partly caused by the damaging effects of increased glandular concentrations of nitric oxide (NO) derived from up-regulation of inducible NO synthase (iNOS) that accompanies glandular inflammation. The present study examines the effects of increased iNOS expression on salivary gland secretory function.

Methods. The inflammogen lipopolysaccharide (LPS) was introduced intraductally into rat submandibular glands, and glandular responsiveness to cholinergic stimulation was determined.

Results. LPS provoked a rapid, long-lasting inflammation, increasing gland weight (by almost 20%) and inflammatory cell infiltration at 3 and 24 h. Immunoblotting of glandular homogenates indicated that iNOS expression was increased ~4-fold, and immunohistochemistry of frozen tissue sections showed increased iNOS expression in acinar cells. Salivary secretion from inflamed glands was significantly increased in response to low doses of methacholine and accompanied by increased acinar cell calcium signalling in vitro. Prior administration of the iNOS inhibitors, aminoguanidine or L-NIL [L-N6-(1-iminoethyl)-lysine dihydrochloride] abolished increased secretion and acinar cell calcium signalling.

Conclusions. Up-regulation of glandular iNOS expression can increase cholinergically evoked salivary secretion and appears to offset any secretory hypofunction linked with glandular inflammation. It seems unlikely that increased glandular levels of NO are responsible for the secretory hypofunction that accompanies SS.

KEY WORDS: Sjögren's syndrome, Salivary gland, Secretory hypofunction, Nitric oxide, Inducible nitric oxide synthase, Cholinergic, Rat submandibular, Lipopolysaccharide

Submitted 9 February 2009; revised version accepted 27 August 2009.
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