Food allergy-induced anaphylaxis impairs adrenal adrenergic biosynthesis despite preserved vagal afferent-adrenal...

Food-induced anaphylaxis is a life-threatening allergic reaction in which endogenous sympathoadrenal responses play a critical role in maintaining physiological homeostasis. However, the functional status of autonomic pathways regulating adrenal catecholamine output during anaphylaxis remains unclear. Using a mouse model of food allergy-induced anaphylaxis, we examined the vagal afferent-medullary C1 neuron-adrenal sympathetic pathway and adrenal adrenergic function. Ovalbumin challenge induced hypotension, hypothermia, metabolic acidosis, and elevated plasma catecholamines. Despite severe systemic deterioration, vagal afferent stimulation and optogenetic activation of C1 neurons continued to evoke robust adrenal sympathetic responses, indicating preserved autonomic regulation. In contrast, adrenal transcriptomic analysis revealed enrichment of hypoxia-related pathways and selective suppression of phenylethanolamine N-methyltransferase (PNMT), a key enzyme for adrenaline synthesis. Oxygen supplementation partially restored PNMT expression, increased plasma adrenaline levels, and improved physiological outcomes. These findings identify hypoxia-associated adrenal dysfunction as a potential limitation of endogenous adrenergic compensation during anaphylactic shock.