Figure 4.

Oxidative stress inhibition reduces MMP activation in hypertension. Uncoupled eNOS and MMPs produce superoxide (O₂⁻) that uses NO for peroxynitrite (ONOO⁻) production causing MMP activation and consequently vascular remodeling and dysfunction. Thus, MMP inhibitors and drugs with antioxidant properties can inhibit MMP activation, improving vascular function and reverting vascular remodeling. Doxycycline has antioxidant effects but also relies on direct inhibition of the active forms of MMPs. Drugs capable of augmenting NO bioavailability are also related to MMP inhibition, but further studies are needed to establish the relation between augmentation in NO (and NO-related species) and MMPs in hypertension.