The engineered CyQ-2 probe enabled in vivo quantification of hypothalamic norepinephrine elevation, which correlated with 74% aortic wall thickening in a hypertensive mouse model.
A novel dual-modal NIR-FLIM probe successfully quantified hypothalamic norepinephrine dynamics in vivo, demonstrating that AT1R blockade with irbesartan normalizes NE levels and reverses vasculopathy in a hypertensive mouse model.
Hypothalamic norepinephrine (NE) dysregulation drives hypertensive pathogenesis, yet lacks precise in vivo quantitative monitoring tools. We engineered CyQs probes integrating near-infrared (NIR) intensity and fluorescence lifetime imaging (FLIM) for spatiotemporal NE tracking. CyQ-2 employs a hemicyanine scaffold conjugated to an S-phenyl carbonate moiety, enabling 16-fold fluorescence turn-on, 0.21 μM detection limit, and 0.8 ns lifetime extension upon NE-specific activation via nucleophilic cyclization. CyQ-2 mapped endogenous NE dynamics in PC12 cells and the K+-evoked neurotransmitter release. In the hypertensive mouse model, FLIM quantified hypothalamic NE elevation, correlating with 74% aortic wall thickening. Critically, Angiotensin II type 1 receptor (AT1R) blockade (irbesartan, IRB) normalized NE levels and reversed vasculopathy. This work establishes a molecular platform linking hypothalamic NE dynamics to vascular pathology, enabling the mechanistic dissection of neurogenic hypertension and the quantitative evaluation of neuromodulation therapies.
Tang et al. (2026) studied Neurogenic Hypertension. CyQ-2 probe was evaluated on Hypothalamic norepinephrine (NE) tracking and quantification. The engineered CyQ-2 probe enabled in vivo quantification of hypothalamic norepinephrine elevation, which correlated with 74% aortic wall thickening in a hypertensive mouse model.