Exp Mol Med.  2012 Dec;44(12):749-755.

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

• Kang YH
• Yang IJ
• Morgan KG
• Shin HM

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 microM)-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 x 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.

Keyword

cinnamyl alcohol; cyclic GMP-dependent protein kinase type I; nitric oxide; potassium channels; rho-associated kinases

MeSH Terms

Animals
Aorta/drug effects/metabolism/physiology
Atrial Natriuretic Factor/pharmacology
Cyclic GMP/*metabolism
Cyclic GMP-Dependent Protein Kinases/*metabolism
Dipeptides/pharmacology
Human Umbilical Vein Endothelial Cells/drug effects/metabolism
Humans
Male
Methylene Blue/pharmacology
NG-Nitroarginine Methyl Ester/pharmacology
Nitric Oxide/*metabolism
Nitric Oxide Synthase/metabolism
Oxadiazoles/pharmacology
Phenylephrine/pharmacology
Phosphorylation
Potassium Channel Blockers/pharmacology
Potassium Channels/*agonists
Propanols/*pharmacology
Quinoxalines/pharmacology
Rats
Rats, Sprague-Dawley
Signal Transduction
Vasoconstriction/*drug effects
Vasodilation/drug effects
rho-Associated Kinases/antagonists & inhibitors/*metabolism