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The effects of upper incisor separation on the submandibular and sublingual glands of rats were examined biochemically, immunohistologically, and radio-immunologically during 28 days of treatment. Lateral separation of the upper incisors by application of force from an orthodontic appliance caused significant enlargement of the sublingual and submandibular glands of rats by three and seven days, respectively, after the beginning of the orthodontic treatment. This enlargement was followed by a significant increase of both RNA and DNA content, with some evidence of hyperplasia and hypertrophy. The enlargement was also associated with a significant increase of substance P at early stages after treatment, suggesting the involvement of the sensory nerves. These changes were largely inhibited by phenoxybenzamine, an alpha-adrenergic blocker, but not by atropine or morphine. Wet weights and RNA contents of the sublingual glands were markedly reduced by atropine. In comparison with control animals, the enlarged submandibular glands of rats subjected to orthodontic treatment secreted additional proteins identical with those secreted by glands enlarged by chronic administration of isoproterenol. In addition, chemical sympathectomy with 6-hydroxydopamine and phenoxybenzamine stimulated the synthesis of these abnormal proteins, but atropine and morphine did not. In contrast, protease activities in the convoluted granular tubule cells in the submandibular glands were increasingly reduced after treatment, as seen in rats subjected to chronic treatment with isoproterenol. However, the submandibular and sublingual glands completely recovered after removal of the orthodontic appliance.

Saliva secreted in response to methoxamine and pilocarpine was collected from the cannulated ducts of the submandibular glands of male and female rats at weekly intervals from two to 10 weeks of age. It was analyzed for volume and for concentrations of protein, potassium, calcium, and inorganic phosphate. Following the collection of saliva, the submandibular glands were removed and weighted. The wet weights of the glands increased substantially up to seven weeks of age and then reached almost plateau values in both sexes. The salivary volumes secreted in response to both agents in both sexes were positively correlated with the gland weights, except that after five to six weeks of age there was no correlation between gland weight and methoxamine-stimulated salivary volume. The concentrations of protein, potassium, and inorganic phosphate were inversely related to the flow rates only at relatively low rates of flow. The concentration of calcium was positively correlated with the protein concentration and was independent of the nature of the stimulus and of sex differences during postnatal development.

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