A novel Danshensu/tetramethylpyrazine derivative induces vasorelaxation on rat aorta and exerts cardioprotection in dogs

ADTM, a previously reported novel Danshensu (DSS)/tetramethylpyrazine (TMP) derivative with cardioprotective and antiplatelet aggregative effects, is a promising therapeutic candidate for ischemic heart diseases. In the present study, ADTM increased coronary blood flow and protected myocardium against ischemic injury in dogs. In addition, the relaxing effect of ADTM on rat thoracic aorta and its underlying mechanisms were examined. ADTM relaxed KCl- and phenylephrine-precontracted arotic rings in a concentration-dependent manner. The relaxation by ADTM was greater than that by DSS, TMP and the mixture of DSS and TMP. ADTM induced endothelium-independent relaxation, which couldn't be abolished by removal of endothelium and the preincubation with inhibitors of nitric oxide synthase (L-NAME) and guanylate cyclase (ODQ). Potassium channel blockers including tetraethylammonium, BaCl2 and glibenclamide failed to inhibit the relaxation by ADTM. In addition, cyclooxygenase (COX), muscarine receptor and β-adrenoceptor were not involved in ADTM-induced vasorelaxation. ADTM inhibited contraction induced by CaCl2 and phenylephrine in Ca2+-free buffer, suggesting that ADTM inhibited both extracellular Ca2+ influx and intracellular Ca2+ release. Taken together, the vasorelaxation of ADTM may be possibly involved in its cardioprotection. ADTM may serve as a promising candidate for the treatment of ischemic heart diseases.