title: Endothelium-independent vasorelaxation effects of 16-O-acetyldihydroisosteviol on isolated rat thoracic aorta.
abstract: OBJECTIVE
  The aim of this study is to investigate the vasorelaxant effect of 16-O-acetyldihydroisosteviol (ADIS) and its underlying mechanisms in isolated rat aorta.
  
  
  METHODS
  Rat aortic rings were isolated, suspended in organ baths containing Kreb's solution, maintained at 37°C, and mounted on tungsten wire and continuously bubbled with a mixture of 95% O2 and 5% CO2 under a resting tension of 1g. The vasorelaxant effects of ADIS were investigated by means of isometric tension recording experiment.
  
  
  RESULTS
  ADIS (0.1μM-3mM) induced relaxation of aortic rings pre-contracted by phenylephrine (PE, 10μM) and KCl (80mM) with intact-endothelium (Emax=79.26±3.74 and 79.88±3.79, respectively) or denuded-endothelium (Emax=88.05±3.69 and 78.22±6.86, respectively). In depolarization Ca(2+)-free solution, ADIS inhibits calcium chloride (CaCl2)-induced contraction in endothelium-denuded rings in a concentration-dependent manner. In addition, ADIS attenuates transient contractions in Ca(2+)-free medium containing EGTA (1mM) induced by PE (10μM) and caffeine (20mM). By contrast, relaxation was not affected by tetraethylammonium (TEA, 5mM), 4-aminopyridine (4-AP, 1mM), glibenclamide (10μM), barium chloride (BaCl2, 1mM), and 1H-[1,2,3]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ, 1μM).
  
  
  CONCLUSIONS
  These findings reveal the vasorelaxant effect of ADIS, through endothelium-independent pathway. It acts as a Ca(2+) channel blocker through both intracellular and extracellular Ca(2+) release.
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 Biochemistry, Faculty of Medical Science, Phayao University, Phayao 56000, Thailand.
authors.forename: Amnart
authors.initials: A
authors.lastname: Onsa-Ard
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: Orawan
authors.initials: O
authors.lastname: Wonganan
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* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D045786:Diterpenes, Kaurane / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: C000594808:16-O-acetyldihydroisosteviol; D002121:Calcium Channel Blockers; D045786:Diterpenes, Kaurane; D014665:Vasodilator Agents; D002122:Calcium Chloride; D002118:Calcium
keywords: 16-O-Acetyldihydroisosteviol; Aorta; Endothelium-independent; Vasorelaxation