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

Gábor Raffai,1 Byungkuk Kim,1 Sanga Park,1 Gilson Khang,1 Dongwon Lee,1 Paul M Vanhoutte1,21World Class University, Department of BIN Fusion Technology, Chonbuk National University, Jeonju, Jeonbuk, South Korea; 2Department of Pharmacology and Pharmacy and State Key Laboratory for Pharma...

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Autores principales:	Raffai G, Kim B, Park S, Khang G, Lee D, Vanhoutte PM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a9738d5b9e75445ebafa26db1993e699
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spelling	oai:doaj.org-article:a9738d5b9e75445ebafa26db1993e6992021-12-02T11:01:34ZCinnamaldehyde and cinnamaldehyde-containing micelles induce relaxation of isolated porcine coronary arteries: role of nitric oxide and calcium1178-2013https://doaj.org/article/a9738d5b9e75445ebafa26db1993e6992014-05-01T00:00:00Zhttp://www.dovepress.com/cinnamaldehyde-and-cinnamaldehyde-containing-micelles-induce-relaxatio-a16929https://doaj.org/toc/1178-2013 Gábor Raffai,1 Byungkuk Kim,1 Sanga Park,1 Gilson Khang,1 Dongwon Lee,1 Paul M Vanhoutte1,21World Class University, Department of BIN Fusion Technology, Chonbuk National University, Jeonju, Jeonbuk, South Korea; 2Department 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, ChinaBackground 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.Keywords: calcium sensitivity, cinnamaldehyde, L-type Ca2+ channel, NO synthase, micelle-forming polymeric prodrug, porcine coronary arteryRaffai GKim BPark SKhang GLee DVanhoutte PMDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 2557-2566 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Raffai G Kim B Park S Khang G Lee D Vanhoutte PM Cinnamaldehyde and cinnamaldehyde-containing micelles induce relaxation of isolated porcine coronary arteries: role of nitric oxide and calcium
description	Gábor Raffai,1 Byungkuk Kim,1 Sanga Park,1 Gilson Khang,1 Dongwon Lee,1 Paul M Vanhoutte1,21World Class University, Department of BIN Fusion Technology, Chonbuk National University, Jeonju, Jeonbuk, South Korea; 2Department 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, ChinaBackground 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.Keywords: calcium sensitivity, cinnamaldehyde, L-type Ca2+ channel, NO synthase, micelle-forming polymeric prodrug, porcine coronary artery
format	article
author	Raffai G Kim B Park S Khang G Lee D Vanhoutte PM
author_facet	Raffai G Kim B Park S Khang G Lee D Vanhoutte PM
author_sort	Raffai G
title	Cinnamaldehyde and cinnamaldehyde-containing micelles induce relaxation of isolated porcine coronary arteries: role of nitric oxide and calcium
title_short	Cinnamaldehyde and cinnamaldehyde-containing micelles induce relaxation of isolated porcine coronary arteries: role of nitric oxide and calcium
title_full	Cinnamaldehyde and cinnamaldehyde-containing micelles induce relaxation of isolated porcine coronary arteries: role of nitric oxide and calcium
title_fullStr	Cinnamaldehyde and cinnamaldehyde-containing micelles induce relaxation of isolated porcine coronary arteries: role of nitric oxide and calcium
title_full_unstemmed	Cinnamaldehyde and cinnamaldehyde-containing micelles induce relaxation of isolated porcine coronary arteries: role of nitric oxide and calcium
title_sort	cinnamaldehyde and cinnamaldehyde-containing micelles induce relaxation of isolated porcine coronary arteries: role of nitric oxide and calcium
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/a9738d5b9e75445ebafa26db1993e699
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_version_	1718396371249135616

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

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