Acute sympathetic stress causes excessive secretion of catecholamines and induces cardiac injuries,which are mainly mediated by β-adrenergic receptors (β-ARs).However,α1-adrenergic receptors (α1-ARs) are also expressed in the heart and are activated upon acute sympathetic stress.In the present study,we investigated whether α1-AR activation induced cardiac inflammation and the underlying mechanisms.Male C57BL/6 mice were injected with a single dose of α1-AR agonist phenylephrine (PE,S or 10 mg/kg,s.c.) with or without pretreatment with α-AR antagonist prazosin (5 mg/kg,s.c.).PE injection caused cardiac dysfunction and cardiac inflammation,evidenced by the increased expression of inflammatory cytokine IL-6 and chemokines MCP-1 and MCP-5,as well as macrophage infiltration in myocardium.These effects were blocked by prazosin pretreatment.Furthermore,PE injection significantly increased the expression of NOD-like receptor protein 3 (NLRP3) and the cleavage of caspase-1 (p20) and interleukin18 in the heart;similar results were observed in both Langendorff-perfused hearts and cultured cardiomyocytes following the treatment with PE (10 μM).Moreover,PE-induced NLRP3 inflammasome activation and cardiac inflammation was blocked in Nlrp3-/-mice compared with wild-type mice.In conclusion,α1-AR overactivation induces cardiac inflammation by activating NLRP3 inflammasomes.