Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, China.
PLoS One. 2012;7(10):e47030. doi: 10.1371/journal.pone.0047030. Epub 2012 Oct 9.
Cajaninstilbene acid (CSA) is a major active component present in the leaves of Cajanus cajan (L.) Millsp. The present study explores the underlying cellular mechanisms for CSA-induced relaxation in rat renal arteries. Vascular reactivity was examined in arterial rings that were suspended in a Multi Myograph System and the expression of signaling proteins was assessed by Western blotting method. CSA (0.1-10 µM) produced relaxations in rings pre-contracted by phenylephrine, serotonin, 9, 11-dideoxy-9α, 11α-epoxymethanoprostaglandin F(2α) (U46619), and 60 mM KCl. CSA-induced relaxations did not show difference between genders and were unaffected by endothelium denudation, nor by treatment with N(G)-nitro-L-arginine methyl ester, indomethacin, ICI-182780, tetraethylammonium ion, BaCl(2), glibenclamide, 4-aminopyridine or propranolol. CSA reduced contraction induced by CaCl(2) (0.01-5 mM) in Ca(2+)-free 60 mM KCl solution and by 30 nM (-)-Bay K8644 in 15 mM KCl solution. CSA inhibited 60 mM KCl-induced Ca(2+) influx in smooth muscle of renal arteries. In addition, CSA inhibited contraction evoked by phorbol 12-myristate 13-acetate (PMA, protein kinase C agonist) in Ca(2+)-free Krebs solution. Moreover, CSA reduced the U46619- and PMA-induced phosphorylation of myosin light chain (MLC) at Ser19 and myosin phosphatase target subunit 1 (MYPT1) at Thr853 which was associated with vasoconstriction. CSA also lowered the phosphorylation of protein kinase C (PKCδ) at Thr505. In summary, the present results suggest that CSA relaxes renal arteries in vitro via multiple cellular mechanisms involving partial inhibition of calcium entry via nifedipine-sensitive calcium channels, protein kinase C and Rho kinase.
鸡纳酸（CSA）是木豆（Cajanus cajan（L.）Millsp）叶片中的一种主要活性成分。本研究探讨了 CSA 诱导大鼠肾动脉舒张的潜在细胞机制。在多肌描记系统中悬浮的动脉环中检查血管反应性，并通过 Western 印迹法评估信号蛋白的表达。CSA（0.1-10μM）可使预先用苯肾上腺素、血清素、9、11-去氧-9α、11α-环氧甲酰基前列腺素 F（2α）（U46619）和 60mM KCl 收缩的环松弛。CSA 诱导的松弛在性别之间没有差异，不受内皮细胞剥脱、N（G）-硝基-L-精氨酸甲酯、吲哚美辛、ICI-182780、四乙铵离子、BaCl（2）、格列本脲、4-氨基吡啶或普萘洛尔的影响。CSA 减少了无钙 60mM KCl 溶液中 CaCl（2）（0.01-5mM）和 15mM KCl 溶液中 30nM（-）-Bay K8644 诱导的收缩。CSA 抑制肾动脉平滑肌中由 60mM KCl 诱导的 Ca（2+）内流。此外，CSA 抑制了无钙 Krebs 溶液中佛波醇 12-肉豆蔻酸 13-乙酸（PKC 激动剂）诱导的收缩。此外，CSA 降低了 U46619 和 PMA 诱导的肌球蛋白轻链（MLC）在 Ser19 和肌球蛋白磷酸酶靶亚单位 1（MYPT1）在 Thr853 的磷酸化，这与血管收缩有关。CSA 还降低了蛋白激酶 C（PKCδ）在 Thr505 的磷酸化。综上所述，本研究结果表明，CSA 通过涉及钙通道阻滞剂敏感钙通道、蛋白激酶 C 和 Rho 激酶的部分抑制，以及蛋白激酶 C 和 Rho 激酶的部分抑制，在体外松弛肾动脉。
