Hydroxysafflor yellow A actives BK Ca channels and inhibits L-type Ca channels to induce vascular relaxation

• Published in: European journal of pharmacology 2020-03, Vol.870, p.172873
• Main Authors: Wang, Na, He, Dongmei, Zhou, Yuanqun, Wen, Jing, Liu, Xiaoqin, Li, Pengyun, Yang, Yan, Cheng, Jun
• Format: Article
• Language: English
• ISSN: 1879-0712

Hydroxy-safflor yellow A (HSYA) can exert a variety of effects upon the vascular system. However, the underlying mechanisms are not clear. The present study is to investigate its vasodilating effect and the mechanisms. Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were enrolled for studying effects of HSYA on blood pressure, vasodilation, intracellular Ca transient and membrane ion channels. Vasodilation and intracellular Ca transient were measured by using vasomotor assay and fluorescence imaging system, respectively. The effect of HSYA on the large conductance Ca activated and voltage-gated potassium channel (BK channel) currents in rat mesentery artery and on L-type calcium channel (Ca-L) currents in HEK293cells expressed with Ca-L were investigated using patch clamp techniques. Blood pressure of SHR and WKY rats were concentration dependently reduced by HSYA with a larger effect of HSYA in SHR than that in WKY rats. The tension of mesenteric arteries induced by 3 μM phenylephrine was attenuated by HSYA (IC  = 90.8 μΜ). Patch clamp study showed that HSYA could activate BK channels and suppress Ca-L channels in a concentration dependent manner. The results of calcium signaling assays indicated that HSYA could reduce the intracellular free Ca level. These findings demonstrate that HSYA could activate BK channels and inhibit Ca-L channels and reduce intracellular free Ca level, which are probably important for its vasodilatory effect.