Department of Pharmacology, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan.
Phytomedicine. 2010 Aug;17(10):760-70. doi: 10.1016/j.phymed.2010.01.003. Epub 2010 Feb 18.
Baicalin isolated from Scutellaria baicalensis is a traditional Chinese herbal medicine used for cardiovascular dysfunction. The ionic mechanism of the vasorelaxant effects of baicalin remains unclear. We investigated whether baicalin relaxes mesenteric arteries (MAs) via large-conductance Ca2+-activated K+ (BK(Ca)) channel activation and voltage-dependent Ca2+ channel (VDCC) inhibition. The contractility of MA was determined by dual wire myograph. BK(Ca) channels and VDCCs were measured using whole-cell recordings in single myocytes, enzymatically dispersed from rat MAs. Baicalin (10-100 microM) attenuated 80 mM KCl-contracted MA in a concentration-related manner. L-NAME (30 microM) and indomethacin (10 microM) little affected baicalin (100 microM)-induced vasorelaxations. Contractions induced by iberiotoxin (IbTX, 0.1 microM), Bay K8644 (0.1 microM) or PMA (10 microM) were abolished by baicalin 100 microM. In MA myocytes, baicalin (0.3-30 microM) enhanced BK(Ca) channel activity in a concentration-dependent manner. Increased BK(Ca) currents were abolished by IbTX (0.1 microM). Baicalin-mediated (30 microM) BK(Ca) current activation was significantly attenuated by an adenylate cyclase inhibitor (SQ 22536, 10 microM), a soluble guanylate cyclase inhibitor (ODQ, 10 microM), competitive antagonists of cAMP and cGMP (Rp-cAMP, 100 microM and Rp-cGMP, 100 microM), and cAMP- and cGMP-dependent protein kinase inhibitors (KT5720, 0.3 microM and KT5823, 0.3 microM). Perfusate with PMA (0.1 microM) abolished baicalin-enhanced BK(Ca) currents. Additionally, baicalin (0.3-30 microM) reduced the amplitude of VDCC currents in a concentration-dependent manner and abolished VDCC activator Bay K8644-enhanced (0.1 microM) currents. Baicalin produced MA relaxation by activating BK(Ca) and inhibiting VDCC channels by endothelium-independent mechanisms and by stimulating the cGMP/PKG and cAMP/PKA pathways.
黄芩素是从黄芩中分离出来的一种中药，用于治疗心血管功能障碍。黄芩素舒张血管的离子机制尚不清楚。我们研究了黄芩素是否通过大电导钙激活钾通道（BK(Ca)) 激活和电压依赖性钙通道（VDCC）抑制来舒张肠系膜动脉（MA）。MA 的收缩性通过双丝肌描记法确定。BK(Ca) 通道和 VDCC 用酶从大鼠 MA 中分散的单个肌细胞中的全细胞记录进行测量。黄芩素（10-100 microM）以浓度相关的方式减弱 80 mM KCl 收缩的 MA。L-NAME（30 microM）和吲哚美辛（10 microM）对黄芩素（100 microM）诱导的血管舒张作用影响不大。由 Iberiotoxin（IbTX，0.1 microM）、Bay K8644（0.1 microM）或 PMA（10 microM）诱导的收缩被 100 microM 黄芩素消除。在 MA 心肌细胞中，黄芩素（0.3-30 microM）以浓度依赖性方式增强 BK(Ca) 通道活性。增加的 BK(Ca) 电流被 IbTX（0.1 microM）消除。黄芩素介导的（30 microM）BK(Ca) 电流激活被腺苷酸环化酶抑制剂（SQ 22536，10 microM）、可溶性鸟苷酸环化酶抑制剂（ODQ，10 microM）、cAMP 和 cGMP 的竞争性拮抗剂（Rp-cAMP，100 microM 和 Rp-cGMP，100 microM）和 cAMP 和 cGMP 依赖性蛋白激酶抑制剂（KT5720，0.3 microM 和 KT5823，0.3 microM）显著减弱。含有 PMA（0.1 microM）的灌流液消除了黄芩素增强的 BK(Ca) 电流。此外，黄芩素（0.3-30 microM）以浓度依赖性方式降低 VDCC 电流的幅度，并消除 VDCC 激活剂 Bay K8644 增强的（0.1 microM）电流。黄芩素通过激活 BK(Ca) 和抑制内皮非依赖性机制的 VDCC 通道，以及通过刺激 cGMP/PKG 和 cAMP/PKA 途径来产生 MA 舒张。
