Protective Effects of Selective β-Adrenoceptor Blockade on Renal Pathophysiology in a Catecholamine Storm of Rat

Excessive administration of epinephrine and norepinephrine in critically ill patients may trigger a catecholamine storm and contribute to acute kidney injury (AKI) through activation of β-adrenoceptor signaling. Although clinical observations link high-dose catecholamine exposure to increased AKI risk, experimental models and mechanistic studies remain limited. We established a rodent model of combined epinephrine and norepinephrine infusion to investigate the renoprotective effects of subtype-selective β-adrenoceptor blockers. Animals received the β1-selective blockers metoprolol or atenolol, or the β2-selective blocker ICI 118,551. β1-adrenoceptor blockade, particularly with metoprolol, significantly attenuated renal histopathological injury and improved biochemical markers of kidney dysfunction. These protective effects were associated with suppression of ferroptosis-related pathways in the renal cortex. Atenolol partially improved biochemical parameters but did not significantly reduce tubulointerstitial damage, whereas β2-adrenoceptor blockade conferred limited functional benefit despite modest morphological improvement. Collectively, our findings indicate that β1-adrenoceptor activation plays a critical role in catecholamine-induced AKI by promoting ferroptosis. Targeting β1-adrenoceptors, especially with metoprolol, may represent a potential therapeutic strategy for preventing renal injury during catecholamine storms.