title: Relaxation effect of a novel Danshensu/tetramethylpyrazine derivative on rat mesenteric arteries.
abstract: Danshen (Radix Salviae miltiorrhizae) and ChuanXiong (Ligusticum wallichii) are two traditional herbal medicines commonly used in China for the treatment of cardiovascular diseases. The active components in Danshen and ChuanXiong are Danshensu (DSS, (R)-3, 4-dihydroxyphenyllactic acid) and tetramethylpyrazine (TMP), respectively. In the present study, a new compound named ADTM, which is a conjugation of DSS and TMP, was synthesized and its effect on the contractility of rat mesenteric arteries was examined. The relaxation effect of ADTM on rat mesenteric arteries was studied using myography. The effects of ADTM on Ca(2+) channels were measured by Ca(2+) imaging and patch-clamp techniques. The results showed that ADTM caused a concentration-dependent relaxation of rat mesenteric arteries. This relaxation effect was not affected by the removal of endothelium or inhibitors of nitric oxide synthase, cyclooxygenase, guanylyl cyclase and adenylyl cyclase. Potassium channel blockers including tetraethylammonium, iberiotoxin, apamin, 4-aminopyridine, BaCl2 and glibenclamide also failed to inhibit the relaxation response to ADTM. ADTM inhibited CaCl2-induced contractions and reduced the Ca(2+) influx in isolated mesenteric arterial muscle cells. Our results suggest that ADTM may be a novel relaxing agent. Its mechanism of action involves the direct blockade of voltage-gated Ca(2+) channels in vascular smooth muscle cells, resulting in a decrease in Ca(2+) influx into the cells.
authors.affiliation: Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong.
authors.forename: Rachel Wai-Sum
authors.initials: RW
authors.lastname: Li
authors.affiliation: Ethnic Drug Screening & Pharmacology Center, Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University, Kunming 650500, China.
authors.forename: C
authors.initials: C
authors.lastname: Yang
authors.affiliation: Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy, Guangzhou 510632, China.
authors.forename: Luchen
authors.initials: L
authors.lastname: Shan
authors.affiliation: Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy, Guangzhou 510632, China.
authors.forename: Zaijun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy, Guangzhou 510632, China.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Y W
authors.initials: YW
authors.lastname: Kwan
authors.affiliation: Institute of Chinese Medical Sciences, University of Macau, Macau, China.
authors.forename: Simon M Y
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Institute of Chinese Medical Sciences, University of Macau, Macau, China.
authors.forename: Maggie P M
authors.initials: MP
authors.lastname: Hoi
authors.affiliation: Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong.
authors.forename: S W
authors.initials: SW
authors.lastname: Chan
authors.affiliation: Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong.
authors.forename: Alex Chun
authors.initials: AC
authors.lastname: Cheung
authors.affiliation: Department of Physiology, The University of Hong Kong, Hong Kong.
authors.forename: K H
authors.initials: KH
authors.lastname: Cheung
authors.affiliation: Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong. Electronic address: gphleung@hkucc.hku.hk.
authors.forename: George P H
authors.initials: GP
authors.lastname: Leung
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007773:Lactates / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011719:Pyrazines / Q000138:chemical synthesis / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: C000607545:ADTM compound; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D007773:Lactates; D011719:Pyrazines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D002118:Calcium
keywords: Calcium channel; Danshensu tetramethylpyrazine; Mesenteric artery; Relaxation