["The Journal of Physiology, EarlyView. ", "\nAbstract figure legend Exacerbated ATP signalling in the carotid body (CB) of spontaneously hypertensive rats (SHRs) arises from expansion of the chemosensory glomus cell compartment and reduced extracellular ATP metabolism, leading to increased purinergic drive. This structural and signalling remodelling enhances CB excitability and contributes to exaggerated chemoreflex‐mediated sympathoexcitation compared with normotensive controls.\n\n\n\n\n\n\n\n\n\nAbstract\nATP acting on P2X3 receptors contributes to carotid body (CB) hyperexcitability in spontaneously hypertensive rats (SHRs). We investigated whether this reflects altered ATP release and/or impaired ATP metabolism. Using in vitro CB preparations, we quantified ATP release in Wistar rats and SHRs (n = 10 each) and found significantly greater ATP release in SHRs (P = 0.00062). Intracellular ATP depletion in dissociated glomus cells was similar between strains (n = 4 each). Morphometric analysis revealed a disproportionate increase in glomus tissue, measured as tyrosine hydroxylase‐positive area, in juvenile SHRs compared with Wistar rats (n = 8 each; P = 5.44 × 10−6). This enlargement was associated with upregulated Epas1 mRNA (n = 8 each), encoding HIF‑2α, a driver of CB hyperplasia. Transcripts for ATP‑degrading enzymes Enpp1, Enpp3 and Entpd2 were also downregulated in SHRs (n = 8 each), suggesting reduced extracellular ATP breakdown. Electrophysiological recordings in vitro and reflex testing in situ showed that topical ATP or α,β‑methylene‐ATP applied to the CB evoked tachypnoea and sympathoexcitation in both strains, but SHRs displayed a greater sympathetic reflex (n = 4 each; P = 0.037), indicating increased sensitivity to purinergic stimulation. In contrast, testing adenosine transmission revealed no difference between strains; adenosine did not contribute to CB hyperexcitability in SHRs (n = 11 each; P = 0.53). Overall, increased ATP release in SHRs likely reflects CB enlargement from glomus cell expansion, compounded by reduced ATP‑degrading enzyme expression, thereby enhancing purinergic drive and chemoreflex sensitivity.\n\n\n\n\n\n\n\n\n\nKey points\n\nThe carotid bodies (CBs) of spontaneously hypertensive rats (SHRs) release more ATP than those of Wistar rats.\nGlomus cell expansion underpins CB hyperplasia and contributes to increased ATP release in juvenile SHRs.\nUpregulated Epas1 (i.e. HIF‐2α) gene expression is likely responsible for CB hyperplasia in SHRs.\nATP transmission is linked to exacerbated chemoreflex sympathoexcitation.\nAdenosine transmission does not contribute to CB hyperexcitability in SHRs.\n\n\n"]