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This review explores the molecular mechanisms underpinning autonomic dysfunction, emphasizing the roles of \u03b2-adrenergic receptor (\u03b2AR) signaling, cyclic AMP (cAMP) compartmentation, and cholinergic regulation. Dysregulated cAMP nanodomain signaling, \u03b2AR desensitization, impaired vagal tone, and maladaptive autonomic nerve remodeling collectively promote structural, electrophysiological, and functional deterioration. Advances in high-resolution imaging and molecular mapping have revealed previously unrecognized pathways governing second-messenger compartmentation and neuromodulatory feedback loops. These insights are driving the development of next-generation therapeutics designed to selectively restore autonomic balance. Promising strategies include isoform-specific phosphodiesterase inhibitors, vagus nerve stimulation, and axonal modulation therapy, which target norepinephrine and acetylcholine pathways while preserving physiological responsiveness. Integrating pharmacological, neuromodulatory, and molecular approaches represents an evolving frontier for cardiovascular therapeutics. Future strategies will benefit from precision mapping of autonomic circuits, patient-specific profiling, and optimization of therapeutic timing. 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