Figure 9.

Schematic diagram of the protective effect of transient receptor potential melastatin subtype 8 (TRPM8) activation by menthol in vascular smooth muscle cell function. On angiotensin II (Ang II) stimulation, the Ca²⁺ concentration in mitochondria [Ca²⁺]_m is increased and the activity of pyruvate dehydrogenase (PDH) is impaired, leading to the dysfunction of mitochondrial oxidative phosphorylation (OXPHOS) and the excessive generation of reactive oxygen species (ROS) in vascular smooth muscle cells. The activation of TRPM8 by menthol couples sarcoplasmic reticulum Ca²⁺ release to mitochondrial Ca²⁺ uptake, which promotes the activity of PDH and OXPHOS, and inhibited ROS production. Preserving mitochondrial function by menthol blunts Ang II–induced [Ca²⁺]_m overload and mitochondrial dysfunction through inhibiting ROS‐triggered Ca²⁺ influx through the L‐type Ca²⁺ channel.