Endothelium‐independent biphasic effects of relaxation and contraction induced by ethyl acetate extract from Morus alba L on rat aortas

Abstract

The objective of the present study was to explore the underlying mechanisms of the biphasic vasoactive effect of ethyl acetate extract from Morus alba L (EMA) on the rat thoracic aortas. Isolated aortic rings were mounted on the organ bath and EMA‐induced vascular tension changes with or without endothelium were measured. Verapamil, heparin sodium, or ruthenium red was introduced to determine the underlying mechanism of vascular effects of EMA. We found that EMA (0.25–32 g/L) produced a concentration‐dependent vasorelaxation both in endothelium‐intact and ‐denuded aortas preconstricted by high K+ (60 mmol/L KCL) or 1 μmol/L phenylephrine (PE). On the contrary, EMA induced vasoconstriction in endothelium‐denuded aortas pretreated with verapamil (1 μmol/L) and preconstricted by PE, which was abolished by ruthenium red (10 μmol/L), but not by heparin sodium (50 mg/L). In endothelium‐denuded aortas, EMA reduced Ca2+ caused contraction after PE or K+ induced a stable contraction in Ca2+‐free solution. The results indicate that among the biphasic vasoactive effects of EMA, the vasorelaxation is greater than the vasoconstriction, and the vasorelaxation is independent on endothelium and at least mediated by inhibition of voltage‐ and receptor‐dependent Ca2+ channels in vascular smooth muscle cells (VSMCs), while the vasoconstriction may involve activation of ryanodine receptor in endoplasmic reticulum of VSMCs. However, the signal transduction pathway between EMA and intracellular Ca2+ transfer need to be further explored.