Decreased vasodilatory effect of Tanshinone ⅡA Sodium Sulfonate on mesenteric artery in hypertension

Zhou, Yuanqun; Liu, Xiaoqin; Zhang, Xiaodong; Wen, Jing; Cheng, Jun; Li, Pengyun; Wang, Na; Zhou, Xiaobo; Xia, Dengning; Yang, Qingqiang; Yang, Yan

doi:10.1016/j.ejphar.2019.04.049

Cited by 10 publications

(9 citation statements)

References 17 publications

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“…Endothelium-denuded third branch of mesenteric artery segments was prepared using procedures that have been described before [11], and the vessel was threaded with stainless steel wires (40 μm) and fixed to the myograph system (Danish Myo Technologies, Aarhus, Denmark) with Tyrode solution (127 mM NaCl, 5.9 mM KCl, 2.4 mM CaCl 2 , 1.2 mM MgCl 2 , 12 mM glucose, 10 mM HEPES, pH = 7.4 with NaOH and aerated with 95% O 2 –5% CO 2 ). Pharmacological compounds were added directly into the organ bath.…”

Section: Methodsmentioning

confidence: 99%

Mechanism of α1-Adrenergic Receptor-Induced Increased Contraction of Rat Mesenteric Artery in Aging Hypertension Rats

et al. 2021

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Introduction: Vasoconstriction is triggered by an increase in intracellular-free calcium concentration. Growing evidence indicates that contraction is also regulated by calcium-independent mechanisms involving RhoA-Rho kinase (ROCK), protein kinase C (PKC), and so on. In this study, we studied the changes of vascular reactivity as well as the underlying signaling pathways in aging spontaneously hypertensive rats (SHRs). Methods: The artery tension induced by α1-adrenergic receptor activator (α1-AR) phenylephrine (PE) was measured in the absence or presence of myosin light chain kinase (MLCK), PKC, and ROCK inhibitors. The α1-AR, PKC, ROCK, phosphorylation of myosin light chain (MLC), and PKC-potentiated phosphatase inhibitors of 17 kDa (CPI-17) of rat mesenteric arteries were analyzed at the mRNA level or protein level. Results: The vascular tension measurements showed that there was a significant increase in the mesenteric artery contraction induced by PE in old SHR. MLCK inhibitor ML-7 can similarly inhibit PE-induced vasoconstriction. PKC inhibitor GF109203X has the weakest inhibitory effect on PE-induced contraction in old SHR. At the presence of ROCK inhibitor H1152, PE-induced contraction was significantly reduced in young Wistar-Kyoto (WKY) rats, but this phenomenon disappeared in other rats. Furthermore, in old SHR the protein expression of α1-AR decreased and phosphorylation of MLC and CPI-17 were upregulated and MLC phosphatase (MLCP) activity was significantly lower. The expressions of PKC were upregulated in SHR and old rats. In addition, the expression of ROCK-1 was decreased and ROCK-2 was significantly upregulated with age in SHR. Conclusion: In aging hypertension, the expression/activity of PKC or ROCK-2/CPI-17 excessively increased, MLCP activity decreased and MLC phosphorylation enhanced, leading to increased α1-AR-induced vasoconstriction.

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Section: Methodsmentioning

confidence: 99%

Mechanism of α1-Adrenergic Receptor-Induced Increased Contraction of Rat Mesenteric Artery in Aging Hypertension Rats

et al. 2021

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“…STS is a clinically approved component to cure certain kinds of cardiovascular-related diseases in China. , Previous reports demonstrated that STS promoted normalization of the cardiovascular structure through maintaining an ion channel steady state and restoring vascular wall, thus offering a potential feasibility of vessel normalization-based cancer therapy. , As shown in Figure A–C, GNR-T/CM-L + NIR showed a significant decrease in vessel number and a noticeable increase in the average vessel area in comparison with the saline group. Without NIR irradiation, TVN of GNR-T/CM-L is much less effective (Figure S16, Supporting Information), probably due to insufficient STS release and accumulation in the tumor sites.…”

Section: Resultsmentioning

confidence: 90%

“…STS is a clinically approved component to cure certain kinds of cardiovascular-related diseases in China. 26,27 Previous reports demonstrated that STS promoted normalization of the Information), probably due to insufficient STS release and accumulation in the tumor sites. Pericyte coverage is a widely applied test to evaluate vascular normalization.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Fever-Inducible Lipid Nanocomposite for Boosting Cancer Therapy through Synergistic Engineering of a Tumor Microenvironment

Qin

Liu

et al. 2020

ACS Appl. Mater. Interfaces

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A fever-mimic response capable of recruiting reprogrammed macrophages holds great potential in the engineering of the tumor microenvironment (TME). Low-temperature photothermal therapy (LT-PTT) can maintain tumors at a fever-like temperature (<45 °C) temporarily; however, it still faces several challenges in efficient regulation of TME because of reciprocal cross-talk between the bypass pathways. Here, we report a synergistic engineering of TME through an enhanced activation of a fever-mimic response based on both LT-PTT and tumor vascular normalization. Such engineering is achieved by a fever-inducible lipid nanocomposite (GNR-T/CM-L), which produces mild heat (∼43 °C) and sequentially releases multicomponents to cooperatively upregulate interferon-gamma under NIR irradiation, forming a bidirectionally closed loop for downstream M1 tumor-associated macrophage polarization and promoting the inhibition of the tumor growth. In proof-of-concept studies, GNR-T/CM-L demonstrated efficient tumor ablation in breast tumor xenograft-bearing mice and significantly prolonged their survival period. It paves an avenue to precisely reprogram TME for efficient cancer therapy through synergistic pathways of creating fever-like responses in the tumor.

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“…Berberine inhibited TRPV4 to reduce calcium influx and to decrease CaM/MLC activity, thereby regulating vascular tightness (Wang et al, 2015). The mechanism of tanshinone IIA sodium sulfonate (DS-201) vasodilation might be related to the activation of largeconductance calcium-dependent potassium channels (BK ca ), making DS-201 a combination therapy candidate with a BK Ca 2+ agonist to treat hypertension (Zhou et al, 2019b). Baicalin has also been shown to activate the BK ca current, cGMP-dependent protein kinase (PKG), and PKA pathways, which increase potassium outflow and promote hyperpolarization of the myocardial cell membrane, resulting in vasodilation (Lin et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effects of Traditional Chinese Medicine on Cardiovascular Diseases: the Central Role of Calcium Signaling

Zhang

et al. 2021

Front. Pharmacol.

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Calcium, as a second messenger, plays an important role in the pathogenesis of cardiovascular diseases (CVDs). The malfunction of calcium signaling in endothelial cells and vascular smooth muscle cells promotes hypertension. In cardiomyocytes, calcium overload induces apoptosis, leading to myocardial infarction and arrhythmias. Moreover, the calcium–calcineurin–nuclear factor of activated T cells (NFAT) pathway is essential for expressing the cardiac pro-hypertrophic gene. Heart failure is also characterized by reduced calcium transient amplitude and enhanced sarcoplasmic reticulum (SR) calcium leakage. Traditional Chinese medicine (TCM) has been used to treat CVDs for thousands of years in China. Because of its multicomponent and multitarget characteristics, TCM's unique advantages in CVD treatment are closely related to the modulation of multiple calcium handling proteins and calcium signaling pathways in different types of cells involved in distinct CVDs. Thus, we systematically review the diverse mechanisms of TCM in regulating calcium pathways to treat various types of CVDs, ranging from hypertrophic cardiomyopathy to diabetic heart disease.

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Decreased vasodilatory effect of Tanshinone ⅡA Sodium Sulfonate on mesenteric artery in hypertension

Cited by 10 publications

References 17 publications

Mechanism of α1-Adrenergic Receptor-Induced Increased Contraction of Rat Mesenteric Artery in Aging Hypertension Rats

Mechanism of α1-Adrenergic Receptor-Induced Increased Contraction of Rat Mesenteric Artery in Aging Hypertension Rats

Fever-Inducible Lipid Nanocomposite for Boosting Cancer Therapy through Synergistic Engineering of a Tumor Microenvironment

Therapeutic Effects of Traditional Chinese Medicine on Cardiovascular Diseases: the Central Role of Calcium Signaling

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