Vasorelaxant effect of isopropyl 3-(3, 4-dihydroxyphenyl)-2-hydroxypropanoate, a novel metabolite from Salvia miltiorrhiza, on isolated rat mesenteric artery.
The present study was designed to investigate the relaxant effect of isopropyl 3-(3, 4-dihydroxyphenyl)-2-hydroxypropanoate (IDHP), a new metabolite from Salvia miltiorrhiza, on rat mesenteric artery. Isolated mesenteric arterial rings were mounted in organ baths and the isometric tension changes were measured continuously by a sensitive myograph system. The results showed that IDHP at concentrations greater than 0.1 nM produced a concentration-dependent relaxation of artery contracted by norepinephrine with pEC(50) of 7.41+/-0.08. Removal of the endothelium did not affect this relaxation, suggesting that IDHP exerted a direct effect on vascular smooth muscle cells. Meanwhile, the vasorelaxant effect of IDHP was unaffected by pre-treatment with ATP-sensitive K(+) channel inhibitor glibenclamide, delayed rectifier K(+) channel inhibitor 4-aminopyridine, inwardly rectifying K(+) channel inhibitor barium chloride and beta-adrenoceptor antagonist propranolol. However, the non-specific K(+) channel inhibitor tetraethylammonium (TEA, 3 mM) produced a rightward shift of 1.8 fold on the concentration-response curve of IDHP. Moreover, IDHP shifted the concentration-response curve of CaCl(2) as well as two receptor-mediated constrictors, phenylephrine and 5-hydroxytryptamine, to the right in a non-parallel manner. In the absence of extracellular Ca(2+), IDHP depressed the contractions induced by norepinephrine and CaCl(2), and the maximal inhibitions were 48.3+/-18.9% and 58.4+/-10.9%, respectively. These results suggest that IDHP exerts a vasorelaxant effect by inhibiting both Ca(2+) release from intracellular stores and Ca(2+) influx through voltage-dependent calcium channels, and receptor-operated calcium channels in vascular smooth muscle cells. In addition, activation of vascular TEA-sensitive K(+) channels may be partially involved in the relaxant effect of IDHP.
Wang
Sheng-Peng
SP
Department of Pharmacology, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, China.
Zang
Wei-Jin
WJ
Kong
Shan-Shan
SS
Yu
Xiao-Jiang
XJ
Sun
Lei
L
Zhao
Xin-Feng
XF
Wang
Shi-Xiang
SX
Zheng
Xiao-Hui
XH
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011422:Propionates / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D019789:Tetraethylammonium; D014664:Vasodilation / Q000187:drug effects
D015220:Calcium Channels; D015221:Potassium Channels; D011422:Propionates; C528033:isopropyl 3-(3, 4-dihydroxyphenyl)-2-hydroxypropanoate; D019789:Tetraethylammonium; D002118:Calcium