Dual-site recognition leads to a ratiometric fluorescent probe for norepinephrine: quantitative detection and visualization for in-depth understanding of hypertension

Abstract

Hypertension is closely associated with the activation of sympathetic nervous system (SNS). Norepinephrine (NE) belongs to the catecholamine family and is the primary neurotransmitter of SNS. Plasma and tissue NE levels serve as biomarkers of sympathetic overdrive in hypertension, providing measurable indicators to guide therapeutic approaches. However, there are only a few reliable tools to simultaneously quantify plasma NE and visualize tissue NE for comprehensive SNS assessment in hypertension. Herein, to selectively recognize the unique L-hydroxyethylamine and catechol moieties of NE, we designed and synthesized a dual-site fluorescent probe that can specifically bind to these two characteristic groups. The recognition process generates a macrocyclic-ring enhanced by silver bridging, accompanied by a ratiometric fluorescence change. The probe enables quantitative NE detection in both plasma and urine, as well as NE visualization in heart, kidney and adrenal gland tissues. Notably, our results demonstrated that spontaneously hypertensive rats (SHR) have higher circulating and tissue NE levels, indicating SNS overactivation. These findings provide a powerful molecular tool for the assessment of SNS activity and offer an in-depth understanding of hypertension.