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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 c...

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Autores principales: Raffai, Gábor, Kim, Byungkuk, Park, Sanga, Khang, Gilson, Lee, Dongwon, Vanhoutte, Paul M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039418/
https://www.ncbi.nlm.nih.gov/pubmed/24904214
http://dx.doi.org/10.2147/IJN.S56578
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author Raffai, Gábor
Kim, Byungkuk
Park, Sanga
Khang, Gilson
Lee, Dongwon
Vanhoutte, Paul M
author_facet Raffai, Gábor
Kim, Byungkuk
Park, Sanga
Khang, Gilson
Lee, Dongwon
Vanhoutte, Paul M
author_sort Raffai, Gábor
collection PubMed
description 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 A(2) 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. 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.
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spelling pubmed-40394182014-06-05 Cinnamaldehyde and cinnamaldehyde-containing micelles induce relaxation of isolated porcine coronary arteries: role of nitric oxide and calcium Raffai, Gábor Kim, Byungkuk Park, Sanga Khang, Gilson Lee, Dongwon Vanhoutte, Paul M Int J Nanomedicine Original Research 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 A(2) 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. 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. Dove Medical Press 2014-05-21 /pmc/articles/PMC4039418/ /pubmed/24904214 http://dx.doi.org/10.2147/IJN.S56578 Text en © 2014 Raffai et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Raffai, Gábor
Kim, Byungkuk
Park, Sanga
Khang, Gilson
Lee, Dongwon
Vanhoutte, Paul M
Cinnamaldehyde and cinnamaldehyde-containing micelles induce relaxation of isolated porcine coronary arteries: role of nitric oxide and calcium
title 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_short 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
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039418/
https://www.ncbi.nlm.nih.gov/pubmed/24904214
http://dx.doi.org/10.2147/IJN.S56578
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