Mechanisms of vasorelaxation induced by Ziziphora clinopodioides Lam. (Lamiaceae) extract in rat thoracic aorta

Aim of the studyZiziphora clinopodioides Lam. (ZC) is widely used in Uyghur folk medicine for the treatment of hypertension diseases in Xinjiang, an autonomous region of China. To provide pharmacological basis for this traditional use, we explored the vasodilating effects of ZC and investigated the underlying mechanisms.Materials and methodsActivity of hexane (ZCHE), dichloromethane (ZCDE) and aqueous (ZCAE) extracts of ZC were evaluated on isolated rat aortic rings pre-contracted with phenylephrine (PE) or high KCl. The mechanisms were evaluated on ZCDE, the most potent extract.ResultsZCDE-induced relaxation in endothelium-intact aortic rings pre-contracted with phenylephrine (PE, 10−6 M) or high KCl (6 × 10−2 M), with respective EC50 values of 0.27 ± 0.03 and 0.34 ± 0.04 g/l. Mechanic removal of the endothelium did not significantly modify ZCDE-induced relaxation. In endothelium-denuded aorta pre-contracted with PE (10−6 M), the vasorelaxant effect of ZCDE was significantly decreased by 4-amino-pyridine (10−3 M), but not by glibenclamide (10−4 M), iberiotoxin (3 × 10−8 M) and thapsigargin (10−7 M). In Ca2+ free solution, ZCDE significantly inhibited extracellular Ca2+-induced contraction in high KCl and PE pre-contracted rings. Additionally ZDCE inhibited the intracellular Ca2+ release sensitive to PE (10−6 M).ConclusionsThe results demonstrate that ZDCE exhibits endothelium-independent vasodilating properties that are mediated by inhibition of extracellular Ca2+ influx through voltage- and receptor-operated Ca2+ channels (VDDCs and ROCCs), by inhibition of Ca2+ release from intracellular stores, and also by the opening of voltage-dependent K+ channels.

Figure optionsDownload as PowerPoint slide