Assessment of the Anti-anginal Effect of Tetramethylpyrazine Using Vasopressin-Induced Angina Model Rats

Cao, Xin; Nakamura, Yuji; Wada, Takeshi; Kishie, Takuya; Enkhsaikhan, Azjargal; Izumi-Nakaseko, Hiroko; Ando, Kentaro; Zhu, Bing-Mei; Xu, Bin; Sugiyama, Atsushi

doi:10.1248/bpb.b16-00059

Cited by 4 publications

(2 citation statements)

References 14 publications

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“…In the current work, intravenous infusion of vasopressin (2 IU/kg, over 1 min) led to acute and sustained suppression in cardiac contractility. Vasopressin angina is widely used model of experimental angina (Cao et al, ). Vasopressin induces angina by constricting coronary arteries leading too cardiac ischemia (Maturi et al, ).…”

Section: Discussionmentioning

confidence: 99%

Mentha longifolia alleviates experimentally induced angina via decreasing cardiac load

2018

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Angina occurs due to imbalance between heart oxygen demand and supply and is associated with serious morbidity and mortality. Here, the possible antianginal effect of Mentha longifolia extract was studied in experimental model of angina. Aerial parts of M. longifolia were extracted, standardized, and given to rats three days before angina. Heart hemodynamics and conductivity were recorded by microtip catheter and surface electrodes. M. longifolia extract significantly alleviated the sustained decline in cardiac contractility after vasopressin exposure. However, M. longifolia did not affect the impaired cardiac dilation after vasopressin. Heart rate was significantly decreased after vasopressin exposure in rats treated with M. longifolia compared with untreated animals. In addition, M. longifolia produced more increase in systolic and diastolic durations after vasopressin exposure compared with untreated animals. Moreover, the plant extract alleviated the ST height changes during vasopressin injection. M. longifolia extract alleviates impaired cardiac function associated with angina through decreasing heart work. Practical applications The present study is the first to study the effect of M. longifolia in an experimental model of angina. M. longifolia alleviated the impaired cardiac contractility associated with angina exposure. The antianginal effect of M. longifolia could be through reducing cardiac load. This can be concluded from the decrease in heart rate and the systolic and diastolic cycles elongation after exposure to vasopressin in animals pretreated with M. longifolia. This helps in reducing the associated cardiac ischemia upon exposure to vasopressin as indicated by ST change. This could provide new directions in the management of the serious angina disease.

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Section: Discussionmentioning

confidence: 99%

Mentha longifolia alleviates experimentally induced angina via decreasing cardiac load

2018

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“…A previous study demonstrated that the direct positive inotropic effect of tetramethylpyrazine in rat cardiac myocytes may be associated with production of NO ( 28 ). Furthermore, pretreatment with tetramethylpyrazine suppressed vasopressin-induced depression of the S-wave level in a rat model of angina, which was not observed following pretreatment with vehicle alone (saline) ( 29 ). This suggested that tetramethylpyrazine ameliorated vasopressin-induced subendocardial ischemia in vivo .…”

Section: Discussionmentioning

confidence: 99%

Suxiao Jiuxin Pill protects cardiomyocytes against mitochondrial injury and alters gene expression during ischemic injury

Ruan

Chen

Wang

et al. 2017

Experimental and Therapeutic Medicine

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Suxiao Jiuxin Pill (SX), a traditional Chinese medicine compound consisting primarily of tetramethylpyrazine and borneol, has been reported to protect against ischemic heart disease. However, the effects of SX on mitochondrial injury and gene expression in various signaling pathways are unclear. The aim of the present study was to investigate the effects of SX on mitochondrial injury and to screen the expression of genes potentially altered by SX using a cell culture model of ischemic injury. Simulated ischemia was established by culturing HL-1 cardiomyocytes in Dulbecco's modified Eagle medium without glucose or serum in a hypoxic chamber containing 95% N2 and 5% CO2 for 24 h. HL-1 cardiomyocytes were divided into 3 groups: Control, ischemic injury and ischemic injury + SX (100 µg/ml; n=3 wells/group). Mitochondrial membrane potential was detected by staining with JC-1 dye. The mRNA expression levels of adenylyl cyclase (Adcy) 1–9, adrenoceptor β1, Akt1, ATPase Na+/K+ transporting subunit β2, calcium voltage-gated channel auxiliary subunit α2δ (Cacna2d)2, Cacna2d3, calcium channel voltage-dependent γ subunit 8, cytochrome C oxidase subunit 6A2 (Cox6a2), fibroblast growth factor receptor (Fgfr) 4, Fgf8, Fgf12, Gnas complex locus, glycogen synthase kinase 3β (Gsk3b), mitogen-activated protein kinase (Mapk)11-14, Mapk kinase kinase kinase 1 (Map4k1), Mas1, nitric oxide synthase 3 (Nos3), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (Pik3ca), phospholipase A2 group 4A, rap guanine nucleotide exchange factor 4 and ryanodine receptor 2 were detected using reverse transcription-quantitative polymerase chain reaction. The protein expression levels of phosphoinositide 3-kinase (PI3K), MAS-1 and phosphorylated-endothelial NOS were also examined by immunofluorescence staining. The decrease in mitochondrial membrane potential in the cell culture model of ischemic injury (P<0.001) was significantly attenuated by SX treatment (P<0.001). Furthermore, increases in the mRNA expression levels of Adcy2 (P<0.05), 3 (P<0.01) and 8 (P<0.05) in the ischemic injury model were significantly attenuated by SX treatment (P<0.01), and SX treatment significantly decreased the mRNA expression levels of Adcy1 (P<0.01) and 6 (P<0.05) in ischemic cells. Decreases in the mRNA expression levels of Cox6a2 (P<0.001), Gsk3b (P<0.01) and Pik3ca (P<0.001) in the ischemic injury model were also significantly attenuated by SX treatment (P<0.05, P<0.01 and P<0.001, respectively). In addition, the decrease in the protein expression of PI3K (P<0.001) was significantly attenuated by SX treatment (P<0.001). The present findings indicate that SX may protect cardiomyocytes against mitochondrial injury and attenuate alterations in the gene expression of Adcy2, 3 and 8, Cox6a2, Gsk3b and Pik3ca during ischemic injury.

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Role of Chinese Herbal Medicines in Regulation of Energy Metabolism in Treating Cardiovascular Diseases

Guan

2019

Chin. J. Integr. Med.

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Assessment of the Anti-anginal Effect of Tetramethylpyrazine Using Vasopressin-Induced Angina Model Rats

Cited by 4 publications

References 14 publications

Mentha longifolia alleviates experimentally induced angina via decreasing cardiac load

Mentha longifolia alleviates experimentally induced angina via decreasing cardiac load

Suxiao Jiuxin Pill protects cardiomyocytes against mitochondrial injury and alters gene expression during ischemic injury

Role of Chinese Herbal Medicines in Regulation of Energy Metabolism in Treating Cardiovascular Diseases

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