Vasodilatory effects of ethanol extract of Radix Paeoniae Rubra and its mechanism of action in the rat aorta

Ethnopharmacological relevance: 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. Aim of the study: 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. Materials and 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-alpha]-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. (C) 2012 Published by Elsevier Ireland Ltd.