Magnesium lithospermate B dilates mesenteric arteries by activating BKCa currents and contracts arteries by inhibiting K(V) currents.
OBJECTIVE
To examine the involvement of K(+) channels and endothelium in the vascular effects of magnesium lithospermate B (MLB), a hydrophilic active component of Salviae miltiorrhiza Radix.


METHODS
Isolated rat mesenteric artery rings were employed to investigate the effects of MLB on KCl- or norepinephrine-induced contractions. Conventional whole-cell patch-clamp technique was used to study the effects of MLB on K(+) currents in single isolated mesenteric artery myocytes.


RESULTS
MLB produced a concentration-dependent relaxation in mesenteric artery rings precontracted by norepinephrine (1 micromol/L) with an EC(50) of 111.3 micromol/L. MLB-induced relaxation was reduced in denuded artery rings with an EC(50) of 224.4 micromol/L. MLB caused contractions in KCl-precontracted artery rings in the presence of N-nitro-L-arginine methyl ester (L-NAME) with a maximal value of 130.3%. The vasodilatory effect of MLB was inhibited by tetraethylammonium (TEA) in both intact and denuded artery rings. In single smooth muscle cells, MLB activated BK(Ca) currents (EC(50) 156.3 micromol/L) but inhibited K(V) currents (IC(50) 26.1 micromol/L) in a voltage- and concentration-dependent manner.


CONCLUSIONS
MLB dilated arteries by activating BK(Ca) channels in smooth muscle cells and increasing NO release from endothelium, but it also contracted arteries precontracted with KCl in the presence of L-NAME.
Zhang
Hai-fei
HF
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Chen
Xue-qing
XQ
Hu
Guo-yuan
GY
Wang
Yi-ping
YP
D000818:Animals; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000378:metabolism; D066298:In Vitro Techniques; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019789:Tetraethylammonium / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation
D004365:Drugs, Chinese Herbal; C494842:Kcnma1 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C061091:lithospermate B; D009569:Nitric Oxide; D019789:Tetraethylammonium; D011189:Potassium Chloride; C064719:iberiotoxin; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine
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