Salvianolic acid B possesses vasodilation potential through NO and its related signals in rabbit thoracic aortic rings.
Salviae miltiorrhizae, a traditional Chinese medicine, is widely used in the treatment of cardiovascular and cerebrovascular diseases. Salvianolic acid B is identified as one of the most important water-soluble active ingredients in Salviae miltiorrhizae and associated with the activation of Ca(2+) channel of cytomembrane. But the further mechanism of action was not very clearly. In our study, we investigated the vasodilation activity of salvianolic acid B using the isolated thoracic aortic rings from Japanese white rabbit. Salvianolic acid B significantly released the contraction of the isolated thoracic aortic rings induced by phenylephrine and CaCl(2) while had no effects on the aortic rings with KCl stimulated. Different with Di-ao-xin-xue-kang capsule, salvianolic acid B caused an increase of Ca(2+) in cytoplasm from not only activation of Ca(2+) channel in cytomembrane but also release of endogenous Ca(2+). Then, a series of endogenous Ca(2+) inhibitors were pretreated to explore the mechanism of salvianolic acid B, and the results provided further evidences that salvianolic acid B causes intracellular calcium release in ryanodine receptors-dependent manners. Moreover, combining l-arginine (l-Arg) with salvianolic acid B promoted the vasodilation activity suggesting a relationship with nitric oxide (NO). To further investigated its mechanism, both guanylate cyclase (GC) inhibitor and NO Synthase inhibitor were used and demonstrated to block vasodilation activity of the aortic rings. Our findings reveal a NO-sGC-cGMP signals dependence mechanism of salvianolic acid B on its vasodilation activity which provide an evidence for its subsequent application in clinic.
Experimental Animal Research Center, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Qiyang
Q
Shou
Yongming
Y
Pan
Xiaoping
X
Xu
Jianqin
J
Xu
Dejun
D
Wang
Yun
Y
Ling
Minli
M
Chen
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D001572:Benzofurans / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011817:Rabbits; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D000071756:Soluble Guanylyl Cyclase; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*; D053630:Depsides
D001572:Benzofurans; D002118:Calcium; D002121:Calcium Channel Blockers; D006152:Cyclic GMP; D004791:Enzyme Inhibitors; D006162:Guanylate Cyclase; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; D000071756:Soluble Guanylyl Cyclase; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C076944:salvianolic acid B; D053630:Depsides