Endothelium-Independent Vasodilatory Effects of Isodillapiolglycol Isolated from Ostericum citriodorum

Ostericum citriodorum is a plant with a native range in China used in herbal medicine for treating angina pectoris. In this study, we investigated the vasodilatory effects of isodillapiolglycol (IDG), which is one of the main ingredients isolated from O. citriodorum ethyl acetate extract, in Sprague–Dawley rat aortic rings, and measured intracellular Ca(2+) ([Ca(2+)](in)) using a molecular fluo-3/AM probe. The results show that IDG dose-dependently relaxed endothelium-intact or -denuded aortic rings pre-contracted with noradrenaline (NE) or potassium chloride (KCl), and inhibited CaCl(2)-induced contraction in high K(+) depolarized aortic rings. Tetraethyl ammonium chloride (a Ca(2+)-activated K(+) channel blocker) or verapamil (an L-type Ca(2+) channel blocker) significantly reduced the relaxation of IDG in aortic rings pre-contracted with NE. In vascular smooth muscle cells, IDG inhibited the increase in [Ca(2+)](in) stimulated by KCl in Krebs solution; likewise, IDG also attenuated the increase in [Ca(2+)](in) induced by NE or subsequent supplementation of CaCl(2). These findings demonstrate that IDG relaxes aortic rings in an endothelium-independent manner by reducing [Ca(2+)](in), likely through inhibition of the receptor-gated Ca(2+) channel and the voltage-dependent Ca(2+) channel, and through opening of the Ca(2+)-activated K(+) channel.