Inducible (calcium-independent) nitric oxide synthase (iNOS) and cyclooxyge
nase-2 (COX-2) are important in the regulation of the function of different
organs during infection. A single dose of lipopolysaccharide (LPS; 5 mg/kg
ip) within 6 h increased NOS activity (20%) and prostaglandin E (PGE) cont
ent (100%) in submandibular glands (SMG) and blocked stimulated salivary se
cretion in adult male rats. The administration of an iNOS synthesis inhibit
or, aminoguanidine (AG), with LPS decreased NOS activity and PGE content. F
urthermore, the administration of meloxicam (MLX), an inhibitor of COX-2, b
locked the increase in PGE and the production of NO. The incubation of slic
es of SMG in the presence of 3-morpholinosydnonimine, a donor of NO, increa
sed the release of PGE highly significantly. The incubation of SMG in the p
resence of a PGE(1) analog (alprostadil) increased the production of NO. Th
ese results indicate that LPS activates NOS, leading to NO release, which a
ctivates COX, generating PGEs that act back to further activate NOS, causin
g further generation of PGEs by activation of COX. Because the alprostadil
administration inhibited stimulated salivation, LPS-induced inhibition of s
alivation appears to be caused by increased PGE production. Diminished sali
vary secretion produces poor oral health; thus the use of COX-2 inhibitors
to counteract the effects of inhibited salivation should be considered.