title: Tetramethylpyrazine, a Chinese drug, blocks coronary vasoconstriction by endothelin-1 and decreases plasma endothelin-1 levels in experimental animals.
abstract: The purpose of this study was to investigate effects of tetramethylpyrazine (TMP), a Chinese plant-derived medicine, on coronary vasoconstriction and related electrocardiographic and histologic changes caused by endothelin-1 (ET-1), and on plasma ET-1 levels. ET-1 (75 pmol) was administered into the left coronary artery (LCA) in anesthetized closed-chest dogs with and without prior infusion of TMP (80 mg/kg). Coronary arterial diameter (CAD) was determined by coronary arteriography (CAG). Blood pressure and electrocardiogram (ECG) were monitored continuously. Histologic damage in tissues was ascertained microscopically. Plasma ET-1 and 6-keto-PGF1 levels were determined by RIA 90 min after i.v. injection of TMP (25 mg/kg; n = 5) in rabbits. Intracoronary injection of ET-1 resulted in a significant vasoconstriction of the entire vascular bed of the LCA, with a decrease in CAD of 35.9 +/- 5.7% (n = 5; p < 0.01) and ischemic changes on ECG and in tissues of endocardium, myocardium, coronary endothelial cells, and capillary vessels. Pretreatment with TMP produced a significant increase in CAD by 38.5 +/- 7.8% (n = 5; p < 0.01) and greatly suppressed the vasoconstriction produced by ET-1. The myocardial tissue damage estimated from the ratio of ischemic area for the entire area after ET-1 injection (35.6%) was completely abolished by TMP (0.6%). In addition, TMP injection induced a significant decrease in plasma ET-1 levels and an increase in 6-keto-PGF1 levels in rabbits. The Chinese medicine TMP could be a useful therapeutic agent in ischemic heart disease by suppressing coronary vasoconstriction and ischemic changes in the tissues produced by ET-1.
authors.affiliation: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zeng
authors.forename: W
authors.initials: W
authors.lastname: Zhu
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.forename: Z
authors.initials: Z
authors.lastname: Jin
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Pan
authors.forename: H
authors.initials: H
authors.lastname: Demura
authors.forename: M
authors.initials: M
authors.lastname: Naruse
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000792:Angiography; D000818:Animals; D003331:Coronary Vessels / Q000033:anatomy & histology / Q000187:drug effects*; D004285:Dogs; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004562:Electrocardiography; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000097:blood* / Q000494:pharmacology; D008297:Male; D011719:Pyrazines / Q000494:pharmacology*; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D004365:Drugs, Chinese Herbal; D019332:Endothelin-1; D011719:Pyrazines; D014665:Vasodilator Agents; D015121:6-Ketoprostaglandin F1 alpha; C017953:tetramethylpyrazine