Parasympathectomy increases resting secretion of the submandibular gland in minipigs in the long term

Parasympathectomy leads to retrogressive alteration and dysfunction of the submandibular gland (SMG) within 1 month, but its long‐term effect is unclear. Excessive secretion is observed in half of the patients 4–6 months after SMG transplantation, which completely denervates the gland. Here, we investigated the long‐term effect of parasympathectomy on the secretion of SMGs in minipigs. The results showed that the resting salivary secretion of SMGs decreased by 82.9% of that in control at 2 months after denervation, but increased by 156% at 6 months. Although experiencing an atrophic period, the denervated glands regained their normal morphology by 6 months. The expression of the function‐related proteins, including muscarinic acetylcholine receptor (mAChR) 3, aquaporin 5 (AQP5), tight junction protein claudin‐3, and claudin‐4 was decreased at 2 months after denervation. Meanwhile, the protein expression of stem cell markers, including sex‐determining region Y‐box 2 and octamer‐binding transcription factor 4, and the number of Ki67+ cells were significantly increased. However, at 6 months after denervation, the expression of mAChR3, AQP5, claudin‐1, claudin‐3, and claudin‐4 was significantly raised, and the membrane distribution of these proteins was increased accordingly. The autonomic axonal area of the glands was reduced at 2 months after denervation but returned to the control level at 6 months, suggesting that reinnervation took place in the long term. In summary, parasympathectomy increases resting secretion of the SMGs in the long term with a possible mechanism involving improved transepithelial fluid transport. This finding may provide a new strategy for xerostomia treatment. Parasympathectomy leads to retrogressive alteration and dysfunction of the submandibular gland (SMG) within 1 month, but its long‐term effect is unclear. In the current study, we demonstrate that the resting saliva secretion of porcine SMG is increased after parasympathectomy in the long term and that the possible mechanism involves the proliferation of ductal cells and improved transepithelial fluid transport. This finding suggests that parasympathectomy might provide a potential novel way to improve the resting secretion of SMGs.