N-Methyl Group Induced Specific Recognition of Epinephrine: Quantitative Detection and Identification for Adrenal Medulla-Driven Hypertension

Identifying the precise etiology of hypertension is critical to achieving targeted blood pressure control. Epinephrine (EP) belongs to the catecholamine family and is the primary hormone secreted by adrenal gland. Plasma and tissue EP levels serve as biomarkers of adrenal overactivation in hypertension, providing measurable indicators to guide therapeutic strategy. However, reliable tools for the simultaneous quantification of plasma EP and visualization of tissue EP remain scarce, limiting comprehensive assessment of adrenal medulla-driven hypertension. Herein, based on the unique N-methyl group in EP, we developed a fluorescent probe using bis-vinylogous thioesters as recognition group to selectively target the characteristic β-hydroxy secondary amine. The probe can specifically bind to EP with high sensitivity, and distinguish EP from analog norepinephrine via the innate steric compression induced by the methyl group of EP. The recognition process generates a five-membered cyclic fluorescent product through a cascade nucleophilic cyclization. The probe enables quantitative EP detection in plasma and EP visualization in adrenal gland tissues. Notably, our results demonstrated that spontaneously hypertensive rats have higher circulating and tissue EP levels, indicating the overactivation of the adrenal medulla. These findings provide a powerful molecular tool for the identification of adrenal medulla-driven hypertension and may support the development of individualized therapies.