title: Vasodilatory effects of cinnamic acid via the nitric oxide-cGMP-PKG pathway in rat thoracic aorta.
abstract: Cinnamic acid (CA) and its derivatives have a broad therapeutic spectrum that includes antimicrobial, antifungal, and antitumoral activities. However, the vasodilative effect of CA has not been demonstrated. The present study characterizes the vasodilative activity and the mechanism of CA in rat thoracic aorta. The vasomotion of aortic strips following CA treatment was measured in an organ bath system. In addition, vascular strips and human umbilical vein endothelial cells (HUVECs) were used in organ bath, Western blot, nitrite, and cyclic guanosine monophosphate (cGMP) measurements. CA relaxed phenylephrine-precontracted aortic strips in an endothelium-dependent manner. Pretreatment of the endothelium-intact aortic strips with N(G) -nitro-l-arginine methyl ester (10(-4)  M), 1 H-[1,2,4]-oxadiazolole-[4,3-a] quinoxalin-10-one, (10(-6)  M) and methylene blue (10(-5)  M) inhibited CA-induced vasorelaxation. CA also increased the phosphorylation of endothelial nitric oxide synthase and nitric oxide generation in a concentration-dependent manner in HUVECs. In addition, cGMP generation and cGMP-dependent protein kinase G (PKG) expression in aortic strips were increased by CA treatment. Furthermore, CA-induced vasorelaxation was inhibited by the PKG inhibitor KT5823 (0.3 μM) and the Ca(2+) -activated K(+) channel inhibitor tetraethylammonium (10(-3)  M). These findings suggest that CA exerts an endothelium-dependent vasodilation effect via the nitric oxide-cGMP-PKG-mediated pathway in rat thoracic aorta.
authors.affiliation: Department of Physiology, College of Oriental Medicine, Dongguk University, Kyungju, Korea.
authors.forename: Yun Hwan
authors.initials: YH
authors.lastname: Kang
authors.forename: Jae Sook
authors.initials: JS
authors.lastname: Kang
authors.forename: Heung Mook
authors.initials: HM
authors.lastname: Shin
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D002934:Cinnamates / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D004727:Endothelium / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D002934:Cinnamates; D014665:Vasodilator Agents; C029010:cinnamic acid; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP