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Exp Mol Med. 2012 Dec 31;44(12):749-55. doi: 10.3858/emm.2012.44.12.083.

Cinnamyl alcohol attenuates vasoconstriction by activation of K⁺ channels via NO-cGMP-protein kinase G pathway and inhibition of Rho-kinase.

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  • 1Department of Physiology College of Oriental Medicine Dongguk University Gyeongju 780-714, Korea.

Abstract

Cinnamyl alcohol (CAL) is known as an antipyretic, and a recent study showed its vasodilatory activity without explaining the mechanism. Here we demonstrate the vasodilatory effect and the mechanism of action of CAL in rat thoracic aorta. The change of tension in aortic strips treated with CAL was measured in an organ bath system. In addition, vascular strips or human umbilical vein endothelial cells (HUVECs) were used for biochemical experiments such as Western blot and nitrite and cyclic guanosine monophosphate (cGMP) measurements. CAL attenuated the vasoconstriction of phenylephrine (PE, 1 μM)-precontracted aortic strips in an endothelium-dependent manner. CAL-induced vasorelaxation was inhibited by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME; 10⁻⁴ M), methylene blue (MB; 10⁻⁵ M) and 1 H-[1,2,4]-oxadiazolole-[ 4,3-a] quinoxalin-10one, (ODQ; 10⁻⁶ or 10⁻⁷ M) in the endothelium-intact aortic strips. Atrial natriuretic peptide (ANP; 10⁻⁸ or 10⁻⁹ M) did not affect the vasodilatory effect of CAL. The phosphorylation of endothelial nitric oxide synthase (eNOS) and generation of nitric oxide (NO) were stimulated by CAL treatment in HUVECs and inhibited by treatment with L-NAME. In addition, cGMP and PKG1 activation in aortic strips treated with CAL were also significantly inhibited by L-NAME. Furthermore, CAL relaxed Rho-kinase activator calpeptin-precontracted aortic strips, and the vasodilatory effect of CAL was inhibited by the ATP-sensitive K⁺ channel inhibitor glibenclamide (Gli; 10⁻⁵ M) and the voltage-dependent K⁺ channel inhibitor 4-aminopyridine (4-AP; 2 × 10⁻⁴ M). These results suggest that CAL induces vasorelaxation by activating K⁺ channels via the NO-cGMP-PKG pathway and the inhibition of Rho-kinase.

PMID:
23178275
[PubMed - indexed for MEDLINE]
PMCID:
PMC3538982
Free PMC Article

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