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.
Highlights
Cinnamyl alcohol (CAL) (Figure 1) is a well-known component of Cinnamomi cortex and C. ramulus (Gong et al, 2004; He et al, 2005)
HASMC and human umbilical vein endothelial cells (HUVECs) cells were treated with CAL (0.4, 0.6, 1 or 2 mM) for 24 h and the cell viability was evaluated
The twig of Cinnamomum cassia is known as Cinnamomi ramulus (CR) and has traditionally been used to improve blood circulation in vascular disease
Summary
CAL (Figure 1) is a well-known component of Cinnamomi cortex and C. ramulus (Gong et al, 2004; He et al, 2005). The plant phenolic CAL is used as a fragrance ingredient and has antipyretic and antiproliferative effects (Letizia et al, 2005; Guo et al, 2006; Ng and Wu, 2011). High blood pressure is closely related to hypertension, arrhythmia, heart failure, and atherosclerosis. For this reason, regulation of vascular tone is very important in the treatment of hypertension-induced vascular diseases. Vascular dilation by relaxation of smooth muscle cells in the blood vessels is an effective means of lowering high blood pressure (Rich, 2009; Félétou et al, 2010)
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