TY - JOUR
T1 - Relaxation effect of a novel Danshensu/tetramethylpyrazine derivative on rat mesenteric arteries
AU - Li, Rachel Wai Sum
AU - Yang, C.
AU - Shan, Luchen
AU - Zhang, Zaijun
AU - Wang, Yuqiang
AU - Kwan, Y.W.
AU - Lee, Simon M.Y.
AU - Hoi, Maggie P.M.
AU - Chan, S.W.
AU - Cheung, Alex Chun
AU - Cheung, K.H.
AU - Leung, George P.H.
N1 - Funding information (Section snippets):
This project was financially supported by Small Project Funding of The University of Hong Kong (Project number: 201209176066).
Publisher copyright:
© 2015 Elsevier B.V.
PY - 2015/8/15
Y1 - 2015/8/15
N2 - 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 Ca2+ channels were measured by Ca2+ 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 Ca2+ 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 Ca2+ channels in vascular smooth muscle cells, resulting in a decrease in Ca2+ influx into the cells.
AB - 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 Ca2+ channels were measured by Ca2+ 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 Ca2+ 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 Ca2+ channels in vascular smooth muscle cells, resulting in a decrease in Ca2+ influx into the cells.
KW - Calcium channel
KW - Danshensu tetramethylpyrazine
KW - Mesenteric artery
KW - Relaxation
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84929580893&partnerID=MN8TOARS
U2 - 10.1016/j.ejphar.2015.04.041
DO - 10.1016/j.ejphar.2015.04.041
M3 - Journal article
SN - 0014-2999
VL - 761
SP - 153
EP - 160
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
ER -
