Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases, Jinan University College of Pharmacy, Guangzhou, China.
Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases, Jinan University College of Pharmacy, Guangzhou, China.
Eur J Pharmacol. 2018 Jan 5;818:158-166. doi: 10.1016/j.ejphar.2017.10.034. Epub 2017 Oct 21.
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, BaCl 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 CaCl and phenylephrine in Ca-free buffer, suggesting that ADTM inhibited both extracellular Ca influx and intracellular Ca 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.
ADTM 是一种以前报道过的新型丹参素（DSS）/四甲基吡嗪（TMP）衍生物，具有心脏保护和抗血小板聚集作用，是缺血性心脏病治疗的有前途的候选药物。在本研究中，ADTM 增加了犬的冠状动脉血流量并保护心肌免受缺血性损伤。此外，还研究了 ADTM 对大鼠胸主动脉的舒张作用及其潜在机制。ADTM 以浓度依赖性方式舒张 KCl 和苯肾上腺素预收缩的主动脉环。ADTM 的舒张作用大于 DSS、TMP 和 DSS 和 TMP 的混合物。ADTM 诱导内皮非依赖性舒张，内皮去除和一氧化氮合酶（L-NAME）和鸟苷酸环化酶（ODQ）抑制剂预孵育不能消除这种舒张作用。包括四乙铵、BaCl 和格列本脲在内的钾通道阻滞剂不能抑制 ADTM 引起的舒张。此外，环氧合酶（COX）、毒蕈碱受体和β-肾上腺素受体不参与 ADTM 诱导的血管舒张。ADTM 在无钙缓冲液中抑制由 CaCl 和苯肾上腺素引起的收缩，表明 ADTM 抑制细胞外 Ca 内流和细胞内 Ca 释放。综上所述，ADTM 的血管舒张作用可能与其心脏保护作用有关。ADTM 可能成为治疗缺血性心脏病的有前途的候选药物。
