Oxidative Neutralization of Nitric Oxide as a Trigger of Coronary Vasospasm: a Peroxynitrite-Centric, Redox–Bistable Framework

Coronary vasospasm may arise not as an isolated event, but as the terminal expression of a redox continuum in which progressive peroxynitrite-driven oxidative neu- tralization of nitric oxide (NO) undermines endothelial control of tone. Objective: To formalize a peroxynitrite-centric mechanism where the instantaneous NO/ROS ratio (rho) governs a bistable transition toward Rho-kinase (ROCK)-dependent Ca2+ sensitization. A minimal kinetic model links NO depletion, ONOO- accumulation, ROCK activation, and macroscopic vasomotor tone. The framework predicts an S-shaped V(rho) curve with hysteresis and reversible switching. As a consequence, coronary vasospasm can be viewed as a redox-bistable transition, not grad- ual vasomotion. Testable signatures include a biochemical threshold, biomarker surges (3-NTup, BH4down, ROCKup), and rapid reversibility by nitrates or ROCK blockade.