title: Cinnamaldehyde and cinnamaldehyde-containing micelles induce relaxation of isolated porcine coronary arteries: role of nitric oxide and calcium.
abstract: OBJECTIVE
  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 Ca(2+) reintroduction in 40 mM KCl Ca(2+)-free solution or by the Ca(2+) 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 Ca(2+) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: World Class University, Department of BIN Fusion Technology, Chonbuk National University, Jeonju, Jeonbuk, South Korea.
authors.forename: Gábor
authors.initials: G
authors.lastname: Raffai
authors.affiliation: World Class University, Department of BIN Fusion Technology, Chonbuk National University, Jeonju, Jeonbuk, South Korea.
authors.forename: Byungkuk
authors.initials: B
authors.lastname: Kim
authors.affiliation: World Class University, Department of BIN Fusion Technology, Chonbuk National University, Jeonju, Jeonbuk, South Korea.
authors.forename: Sanga
authors.initials: S
authors.lastname: Park
authors.affiliation: World Class University, Department of BIN Fusion Technology, Chonbuk National University, Jeonju, Jeonbuk, South Korea.
authors.forename: Gilson
authors.initials: G
authors.lastname: Khang
authors.affiliation: World Class University, Department of BIN Fusion Technology, Chonbuk National University, Jeonju, Jeonbuk, South Korea.
authors.forename: Dongwon
authors.initials: D
authors.lastname: Lee
authors.affiliation: World Class University, Department of BIN Fusion Technology, Chonbuk National University, Jeonju, Jeonbuk, South Korea ; Department of Pharmacology and Pharmacy and State Key Laboratory for Pharmaceutical Biotechnology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Special Administrative Region, China.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Vanhoutte
mesh_terms: D000171:Acrolein / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004655:Emulsions / Q000737:chemistry*; D066298:In Vitro Techniques; D008823:Micelles; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D017942:Nitric Acid / Q000737:chemistry*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D004655:Emulsions; D008823:Micelles; D014665:Vasodilator Agents; D017942:Nitric Acid; D000171:Acrolein; C012843:cinnamaldehyde; D002118:Calcium
keywords: L-type Ca2+ channel; NO synthase; calcium sensitivity; cinnamaldehyde; micelle-forming polymeric prodrug; porcine coronary artery