Involvements of calcium channel and potassium channel in Danshen and Gegen decoction induced vasodilation in porcine coronary LAD artery.
Danshen (Salviae Miltiorrhizae Radix) and Gegen (Puerariae Lobatae Radix) have been widely used in treating cardiovascular diseases for thousands of years in China. The present study was carried out to evaluate the effects of a Danshen and Gegen decoction (DG) on the vascular reactivity of a porcine isolated coronary artery and the underlying mechanisms involved. Porcine coronary rings were precontracted with 15 nM U46619. The involvement of endothelium-dependent mechanisms was explored by removing the endothelium; the involvement of potassium channels was investigated by the pretreatment of the artery rings with various blockers, and the involvement of the calcium channels was investigated by incubating the artery rings with Ca²⁺-free buffer and priming them with high [K⁺] prior to adding CaCl₂ to elicit contraction. The involvement of Ca²⁺ sensitization was explored by evaluating the Rho-activity expression. The results revealed that DG elicited a concentration-dependent relaxation on a U46619-precontracted coronary artery ring. These relaxation responses were not altered by the pretreatment of inhibitors of endothelium-related dilator synthases, cGMP and cAMP pathway inhibitors, potassium channel (BK(Ca), SK(Ca), K(V) and K(ATP)) blockers and endothelium removal. The K(IR) channel blocker BaCl₂ only slightly attenuated the DG-induced relaxation. However, the Ca²⁺-induced artery contraction was inhibited by DG. Additionally, the expression of the phosphorylated myosin light chain was inhibited by DG whereas the activity of RhoA was not affected. Therefore, DG could be a useful cardioprotective agent for vasodilation in patients who have hypertension.
Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
Fan
F
Hu
Chi Man
CM
Koon
Judy Yuet Wa
JY
Chan
Kit Man
KM
Lau
Y W
YW
Kwan
Kwok Pui
KP
Fung
D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002122:Calcium Chloride; D002712:Chlorides / Q000494:pharmacology; D003331:Coronary Vessels; D000242:Cyclic AMP / Q000037:antagonists & inhibitors; D006152:Cyclic GMP / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D029908:Pueraria; D027561:Salvia miltiorrhiza; D015398:Signal Transduction; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D017609:Barium Compounds; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002712:Chlorides; D004365:Drugs, Chinese Herbal; D018994:Myosin Light Chains; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014665:Vasodilator Agents; C024986:barium chloride; C028972:dan-shen root extract; D000242:Cyclic AMP; D020742:rhoA GTP-Binding Protein; D006152:Cyclic GMP; D002122:Calcium Chloride