title: Vasodilatory effects of ethanol extract of Radix Paeoniae Rubra and its mechanism of action in the rat aorta.
abstract: BACKGROUND
  Radix Paeoniae Rubra (RPR) is an important traditional Chinese medicine (TCM) commonly used in clinic for a long history in China. RPR is the radix of either Paeonia lactiflora Pall. or Paeonia veitchii Lynch. RPR has a wide variety of pharmacological actions such as anti-thrombus, anti-coagulation, and anti-atherosclerotic properties, protecting heart and liver. However, the mechanisms involved are to be defined.
  
  
  OBJECTIVE
  The aim of the present study was to define the effect of Paeonia lactiflora Pall. extracts on vascular tension and responsible mechanisms in rat thoracic aortic rings.
  
  
  METHODS
  Ethanol extract of Paeonia lactiflora Pall. (EPL) was examined for their vascular relaxant effects in isolated phenylephrine-precontracted rat thoracic aorta.
  
  
  RESULTS
  EPL induced relaxation of the phenylephrine-precontracted aortic rings in a concentration-dependent manner. Vascular relaxation induced by EPL was significantly inhibited by removal of the endothelium or pretreatment of the rings with N(G)-nitro-L-arginine methylester (L-NAME) or 1H-[1,2,4]-oxadiazolo-[4,3-α]-quinoxalin-1-one (ODQ). Extracellular Ca²⁺ depletion or diltiazem significantly attenuated EPL-induced vasorelaxation. Modulators of the store-operated Ca²⁺ entry (SOCE), thapsigargin, 2-aminoethyl diphenylborinate and Gd³⁺, and an inhibitor of Akt, wortmannin, markedly attenuated the EPL-induced vasorelaxation. Further, the EPL-induced vasorelaxation was significantly attenuated by pretreatment with tetraethylammonium, a non-selective K(Ca) channels blocker, or glibenclamide, an ATP-sensitive K⁺ channels inhibitor, respectively. Inhibition of cyclooxygenases with indomethacin, and adrenergic and muscarinic receptors blockade had no effects on the EPL-induced vasorelaxation.
  
  
  CONCLUSIONS
  The present study suggests that EPL relaxes vascular smooth muscle via endothelium-dependent and Akt- and SOCE-eNOS-cGMP-mediated pathways through activation of both K(Ca) and K(ATP) channels and inhibition of L-type Ca²⁺ channels.
authors.affiliation: Institute of Materia Medica, Taishan Medical University, Taian, Shandong 271016, China. snjin0504@yahoo.com.cn
authors.forename: Song Nan
authors.initials: SN
authors.lastname: Jin
authors.forename: Jin Fu
authors.initials: JF
authors.lastname: Wen
authors.forename: Ting Ting
authors.initials: TT
authors.lastname: Wang
authors.forename: Dae Gill
authors.initials: DG
authors.lastname: Kang
authors.forename: Ho Sub
authors.initials: HS
authors.lastname: Lee
authors.forename: Kyung Woo
authors.initials: KW
authors.lastname: Cho
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D020746:Calcium Channels, L-Type / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D000431:Ethanol / Q000737:chemistry; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D029596:Paeonia; D010936:Plant Extracts / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D020746:Calcium Channels, L-Type; D010936:Plant Extracts; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014665:Vasodilator Agents; D000431:Ethanol