title: Ethyl rosmarinate relaxes rat aorta by an endothelium-independent pathway.
abstract: Ethyl rosmarinate is an ester derivative of rosmarinic acid, a major constituent of Hyptis suaveolens. The present study investigated the vasorelaxant mechanism of ethyl rosmarinate in isolated rat aortic rings using an organ bath system. Ethyl rosmarinate (0.1 µM-3mM) produced concentration-dependent relaxation in aortic rings pre-contracted with phenylephrine (10 µM), exhibiting a pD2 value of 4.56 ± 0.08 and an Emax value of 93.82 ± 5.00% (in endothelium-intact rings), as well as a pD2 value of 4.42 ± 0.05 and an Emax value of 92.10 ± 3.78% (in endothelium-denuded rings). In the endothelium-denuded rings, the vasorelaxant effect of ethyl rosmarinate was reduced by only 4-aminopyridine (1mM); however, this was not the case with tetraethylammonium (5mM), glibenclamide (10 µM), barium chloride (1mM), and 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (ODQ, 1 µM). Ethyl rosmarinate also reduced the contraction induced by phenylephrine (10 µM) and caffeine (20mM) in a Ca(2+)-free solution, and inhibited the contraction induced by increasing extracellular Ca(2+) influx, which was induced by KCl (80 mM). Ethyl rosmarinate (10 µM) inhibits concentration-response curves for phenylephrine, while in the same concentration of ethyl rosmarinate has no effect on contractions induced by increasing concentrations of calcium in the presence of high extracellular potassium. Our results suggests that ethyl rosmarinate induces relaxation in aortic rings via an endothelium-independent pathway, which involves the opening of voltage-gated potassium (Kv) channels and the blockade of both Ca(2+)release from intracellular stores and extracellular Ca(2+) influx. Moreover, ethyl-rosmarinate acts on the extracellular Ca(2+) influx inhibition by interacting with voltage-operated calcium channels (VOCCs) and receptor-operated calcium channels (ROCCs).
authors.affiliation: Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors.forename: Piyawadee
authors.initials: P
authors.lastname: Wicha
authors.affiliation: Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors.forename: Jiraporn
authors.initials: J
authors.lastname: Tocharus
authors.affiliation: Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand.
authors.forename: Archawin
authors.initials: A
authors.lastname: Nakaew
authors.affiliation: Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors.forename: Rungusa
authors.initials: R
authors.lastname: Pantan
authors.affiliation: Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand.
authors.forename: Apichart
authors.initials: A
authors.lastname: Suksamrarn
authors.affiliation: Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. Electronic address: chainarongt@hotmail.com.
authors.forename: Chainarong
authors.initials: C
authors.lastname: Tocharus
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D002934:Cinnamates / Q000494:pharmacology*; D053630:Depsides / Q000494:pharmacology*; D004730:Endothelium, Vascular; D004952:Esters; D066298:In Vitro Techniques; D008297:Male; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D000097123:Rosmarinic Acid
chemical_list: D002934:Cinnamates; D053630:Depsides; D004952:Esters; D014665:Vasodilator Agents; D000097123:Rosmarinic Acid
keywords: Endothelium-independent; Ethyl rosmarinate; Hypertension; Rat aorta; Vasorelaxation