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 CaCl2 as well as two receptor-mediated constrictors, phenylephrine and 5-hydroxytryptamine, to the right in a non-parallel manner. In the absence of extracellular Ca2+, IDHP depressed the contractions induced by norepinephrine and CaCl2, 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 Ca2+ release from intracellular stores and Ca2+ 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. (c) 2007 Elsevier B.V. All rights reserved.