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.

Screening and identification ofMonacusstrain with high TMP production and statistical optimization of its culture medium composition and liquid state fermentation conditions using response surface methodology (RSM)

“…Screening and identification of Monacus strain with high TMP production and statistical optimization of its culture medium composition and liquid state fermentation conditions using response surface methodology (RSM) Figure 1) is one of the main active ingredients of Rhizoma Chuanxiong, Zingiberaceae Curcuma rhizomes and Euphorbiaceae Jatropha stems [1]. Previous studies have evidenced that TMP has the pharmacological activity of anti-platelet aggregation and the physiological functions of softening the blood vessels, increasing coronary blood flow, improving microcirculation and scavenging free radicals [2][3][4][5].…”

Tetramethylpyrazine suppresses interleukin-8 expression in LPS-stimulated human umbilical vein endothelial cell by blocking ERK, p38 and nulear factor-κB signaling pathways

“…TMP has been synthesized and used widely in oriental medicine to effectively treat several cardiovascular complications, including angina pectoris, cerebrovascular and thrombotic vascular diseases (Guo et al, 1983;Dai and Bache, 1985;Zeng et al, 1998), due to its biological activities including vasodilation (Dai and Bache, 1985) and antiplatelet aggregation (Liu and Sylvester, 1990). In recent years, several pharmacological actions produced by TMP have been performed.…”

Protection by Tetramethylpyrazine in Acute Absolute Ethanol-Induced Gastric Lesions

“…It has been considered a true calcium antagonist [1,12] and could be used clinically as a useful therapeutic agent in ischemic heart disease. In other tissues, it acts to suppress coronary vasoconstriction and ischemic changes produced by endothelin-1 [24]. TMP has also been reported as a drug to treat cardiovascular disease [8,9].…”