Functional Dose-Response Effects of Adrenaline on Skeletal MusclePerformance (PHASE II)

Abstract

Background: Adrenaline enhances skeletal muscle performance during stress and exercise, but the dose-response relationship and underlying mechanisms remain incompletely characterized.

Objective: To investigate the dose-response effects of adrenaline on skeletal muscle fatigue resistance and identify the optimal functional dose.

Methods: Frog gastrocnemius-sciatic nerve preparations were treated with saline (Control) or adrenaline at 0.01, 0.1, 0.5, or 1.0 mg/kg. Contractile function (n=40) and biochemical parameters including energy metabolites, glycogenolytic enzymes, signaling molecules, and ionic regulators (n=30) were measured. Integrated analyses including correlation, multiple regression, and path analysis were performed.

Results: Adrenaline produced significant dose-dependent improvements in force generation (+26%), fatigue resistance (T50 +49%), and recovery capacity (+32%), with maximal effects at 0.5 mg/kg. Biochemical analyses revealed increased phosphorylase activity (+20.3%), cAMP elevation (+41.2%), decreased PCr/Pi ratio (-15.5%), and enhanced Na⁺/K⁺-ATPase activity (+5.9%). The 1.0 mg/kg dose showed diminished effects across 78% of parameters, confirming a biphasic inverted-U relationship. Multiple regression identified plasma adrenaline and PCr/Pi ratio as the strongest predictors of fatigue resistance (R²=0.87). Path analysis confirmed a hierarchical mechanism: Adrenaline → β₂-receptor → cAMP → Phosphorylase → PCr/Pi → Functional improvement.

Conclusion: Adrenaline enhances skeletal muscle fatigue resistance through integrated β₂-adrenergic signaling, metabolic activation, and ionic regulation. The optimal dose (0.5 mg/kg) produces maximal functional benefits, while supra-maximal doses reduce efficacy through receptor desensitization and metabolic overload. These findings provide a mechanistic framework for understanding catecholamine modulation of muscle function.