Biphasic effects of sodium danshensu on vessel function in isolated rat aorta.
OBJECTIVE
To investigate the effects of sodium danshensu on vessel function in isolated rat aortic ring.


METHODS
Thoracic aortae from normal rats were isolated and equilibrated in organ bath with Krebs-Henseleit buffer and ring tension was recorded. Effects of sodium danshensu on basal tonus of the vessel and its effects on vessel contraction and relaxation with or without endothelium were observed.


RESULTS
In thoracic arteries under basal tonus, sodium danshensu (0.3-3 g/L) produced a dose-dependent transient contraction. In phenylephrine-precontracted thoracic arteries with or without endothelium, low concentration (0.1-0.3 g/L) of sodium danshensu produced a weak contraction, while high concentrations (1-3 g/L) produced a pronounced vasodilator after a transient vasocontraction. Pre-incubation with sodium danshensu could inhibit vessel contraction induced by phenylephrine and potassium chloride in a concentration-dependent way. Sodium danshensu inhibited phenylephrine- and CaCl(2)-induced vasoconstriction in Ca(2+)-free medium. Pre-incubation with tetraethylammonium, a non-selective K(+) channel blocker, and apamin, a small-conductance calcium-activated K(+) channel blocker partially antagonized the relaxation response induced by sodium danshensu. However, iberiotoxin (big-conductance calcium-sensitive K(+) channel blocker), barium chloride (inward rectifier K(+) channel blocker), and glibencalmide (ATP-sensitive K(+) channel blocker) had no influence on the vasodilation effect of sodium danshensu.


CONCLUSIONS
Sodium danshensu showed a biphasic effects on vessel tension. While low dosage of sodium danshensu produced small contraction possibly through transient enhancement of Ca(2+) influx, high dosage produced significant vasodilation mainly through promoting the opening of non-selective K(+) channels and small-conductance calcium-sensitive K(+) channels in the vascular smooth muscle cells.
New Drug Research Center, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Ning
N
Zhang
Hao
H
Zou
Lei
L
Jin
Jian
J
Wang
Mei-fang
MF
Zhong
Peng
P
Huang
Bing-qing
BQ
Gu
Shi-long
SL
Mao
Chuan
C
Zhang
Hong
H
Chen
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002122:Calcium Chloride / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D007773:Lactates / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011189:Potassium Chloride / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D004365:Drugs, Chinese Herbal; D007773:Lactates; D026902:Potassium Channel Blockers; C035055:3,4-dihydroxyphenyllactic acid; D011189:Potassium Chloride; D006152:Cyclic GMP; D002122:Calcium Chloride; D002118:Calcium