Inhibitory effects of ferulic acid on the contraction responses of porcine coronary arteries: a comparison with diltiazem

Ferulic acid (FA) exerts protective effects against cardiovascular-related diseases; however, its role in coronary artery dilation is unclear. Here, we examined the effects and underlying mechanisms of FA in response to contractions induced by spasmogenic candidates in porcine coronary arteries (PCAs). FA (3 × 10⁻⁴–3 × 10⁻³ M) inhibited high-KCl-induced contractions in a concentration-dependent manner, and FA (3 × 10⁻⁴–10⁻³ M) inhibited high-KCl-induced increases in intracellular Ca²⁺ concentrations in A7r5 cells. FA (3 × 10⁻³ M) showed greater inhibition than diltiazem (3 × 10⁻⁵ M) against chemical-induced contractions but weaker inhibition against high-KCl-induced contractions. FA (3 × 10⁻⁴–3 × 10⁻³ M) inhibited contractions induced by endothelin-1 (10⁻⁸ M) and NaF (10⁻² M) under Ca²⁺-free conditions in a concentration-dependent manner; these contractions were fully suppressed by ML-7 (10⁻⁴ M, a myosin light chain kinase inhibitor). FA (3 × 10⁻³ M) also inhibited myosin light chain phosphorylation induced by NaF (10⁻² M) in A7r5 cells regardless of extracellular Ca²⁺ conditions. These findings indicate that FA inhibits PCA contractions induced by coronary spasmogens by inhibiting L-type Ca²⁺ channels and intracellular routes responsible for extracellular Ca²⁺ influx-independent contractions. The latter mechanism may involve the inhibition of myosin light chain phosphorylation-related processes.