Cinnamaldehyde and cinnamaldehyde-containing micelles induce relaxation of isolated porcine coronary arteries: Role of nitric oxide and calcium

Background and purpose: Cinnamaldehyde, a major component of cinnamon, induces the generation of reactive oxygen species and exerts vasodilator and anticancer effects, but its short half-life limits its clinical use. The present experiments were designed to compare the acute relaxing properties of cinnamaldehyde with those of self-assembling polymer micelles either loaded with cinnamaldehyde or consisting of a polymeric prodrug [poly(cinnamaldehyde)] that incorporates the compound in its backbone. Methods: Rings of porcine coronary arteries were contracted with the thromboxane A₂ receptor agonist U46619 or 40 mM KCl, and changes in isometric tension were recorded. Results: Cinnamaldehyde induced concentration-dependent but endothelium-independent, nitric oxide synthase (NOS)-independent, cyclooxygenase-independent, soluble guanylyl cyclase (sGC)-independent, calcium-activated potassium-independent, and TRPA1 channel-independent relaxations. Cinnamaldehyde also inhibited the contractions induced by 40 mM KCl Ca²⁺ reintroduction in 40 mM KCl Ca²⁺-free solution or by the Ca²⁺ channel opener Bay K8644. Cinnamaldehyde-loaded control micelles induced complete, partly endothelium-dependent relaxations sensitive to catalase and inhibitors of NOS or sGC, but not cyclooxygenase or TRPA1, channels. Cinnamaldehyde-loaded micelles also inhibited contractions induced by 40 mM KCl Ca²⁺ reintroduction or Bay K8644. Poly(cinnamaldehyde) micelles induced only partial, endothelium-dependent relaxations that were reduced by inhibitors of NOS or sGC and by catalase and the antioxidant tiron, but not by indomethacin or TRPA1 channel blockers. Conclusion: The present findings demonstrate that cinnamaldehyde-loaded and poly(cinnamaldehyde) micelles possess vasodilator properties, but that the mechanism underlying the relaxation that they cause differs from that of cinnamaldehyde, and thus could be used both to relieve coronary vasospasm and for therapeutic drug delivery.