scholarly journals Ginsenoside Rb1 Attenuates Agonist-Induced Contractile Response via Inhibition of Store-Operated Calcium Entry in Pulmonary Arteries of Normal and Pulmonary Hypertensive Rats

2015 ◽  
Vol 35 (4) ◽  
pp. 1467-1481 ◽  
Author(s):  
Rui-Xing Wang ◽  
Rui-Lan He ◽  
Hai-Xia Jiao ◽  
Mao Dai ◽  
Yun-Ping Mu ◽  
...  
Keyword(s):  
Contractile Response ◽  
Pulmonary Arteries ◽  
Cyclopiazonic Acid ◽  
Right Heart Failure ◽  
Ginsenoside Rb1 ◽  
Right Heart ◽  
Store Operated Calcium Entry ◽  
Pulmonary Arterial ◽  
Arterial Smooth Muscle Cells ◽  
Pulmonary Arterial Smooth Muscle

Background: Pulmonary hypertension (PH) is characterized by sustained vasoconstriction, enhanced vasoreactivity and vascular remodeling, which leads to right heart failure and death. Despite several treatments are available, many forms of PH are still incurable. Ginsenoside Rb1, a principle active ingredient of Panax ginseng, exhibits multiple pharmacological effects on cardiovascular system, and suppresses monocrotaline (MCT)-induced right heart hypertrophy. However, its effect on the pulmonary vascular functions related to PH is unknown. Methods: We examined the vasorelaxing effects of ginsenoside Rb1 on endothelin-1 (ET-1) induced contraction of pulmonary arteries (PAs) and store-operated Ca2+ entry (SOCE) in pulmonary arterial smooth muscle cells (PASMCs) from chronic hypoxia (CH) and MCT-induced PH. Results: Ginsenoside Rb1 elicited concentration-dependent relaxation of ET-1-induced PA contraction. The vasorelaxing effect was unaffected by nifedipine, but abolished by the SOCE blocker Gd3+. Ginsenoside Rb1 suppressed cyclopiazonic acid (CPA)-induced PA contraction, and CPA-activated cation entry and Ca2+ transient in PASMCs. ET-1 and CPA-induced contraction, and CPA-activated cation entry and Ca2+ transients were enhanced in PA and PASMCs of CH and MCT-treated rats; the enhanced responses were abolished by ginsenoside Rb1. Conclusion: Ginsenoside Rb1 attenuates ET-1-induced contractile response via inhibition of SOCE, and it can effectively antagonize the enhanced pulmonary vasoreactivity in PH.

scholarly journals Risk stratification in PAH

2020 ◽  
Vol 2020 (1) ◽  
Author(s):  
Paul A Corris
Keyword(s):  
Heart Failure ◽  
Pulmonary Arteries ◽  
Right Heart Failure ◽  
Response To Therapy ◽  
Pulmonary Vasculature ◽  
Short Term ◽  
Right Heart ◽  
Term Survival ◽  
Pulmonary Arterial ◽  
Short Term Survival

[No abstract. Showing first paragraph of article]Pulmonary arterial hypertension (PAH) is a chronic disease of the pulmonary vasculature characterized by progressive narrowing of the pulmonary arteries leading to increased pulmonary vascular resistance, right heart failure, and ultimately premature death.There has been a significant improvement in the available medical therapeutic options in this field that have impacted the short-term survival and morbidity in these patients. However, the median survival post-diagnosis remains unacceptable at 7 years.Physicians’ ability to predict PAH disease progression and risk allows them to determine the patient’s prognosis, make informed adjustments to therapy, and monitor his or her response to therapy . If widely adopted, risk prediction can enhance the consistency of treatment approaches and improve the timeliness of referral for lung transplantation. This approach should lead optimal, directed care that ultimately reduces morbidity and improves mortality in patients with PAH.

Staurosporine aglycone bilaterally regulates ERK1/2 phosphorylation in rat pulmonary arterial smooth muscle cells

2008 ◽  
Vol 86 (7) ◽  
pp. 424-430
Author(s):  
Jianing Zhang ◽  
Xiaobo Tang ◽  
Changlian Lu ◽  
Lei Guo ◽  
Shuang Zhang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Smooth Muscle Cells ◽  
Pulmonary Arteries ◽  
Muscle Cells ◽  
Arterial Smooth Muscle ◽  
Pulmonary Arterial ◽  
Arterial Smooth Muscle Cells ◽  
Pulmonary Arterial Smooth Muscle ◽  
Staurosporine Aglycone

Staurosporine, a protein kinase C (PKC) inhibitor, has been reported to regulate the phosphorylation of ERK1/2 in several cell lines. It is still unknown, however, whether its derivative staurosporine aglycone (SA) has the same effect on ERK1/2 activation. In this study, we investigated the effect of SA on ERK1/2 activity in rat pulmonary arteries and pulmonary arterial smooth muscle cells (PASMCs). The pulmonary arteries and PASMCs were treated with SA at different time points and concentrations, and the activation of ERK1/2 was analyzed by Western blotting. The results showed that SA at nanomolar concentrations suppressed ERK1/2 phosphorylation through the PKC pathway alone, but SA at 30 µmol/L for 2 h enhanced the phosphorylation of ERK1/2. The activation of ERK1/2 was inhibited by the MAPK/ERK kinase inhibitor PD98059 or the protein kinase A (PKA) activator isoproterenol. Together, these results suggest that SA has a strong dual regulating effect on ERK1/2 through the PKC and (or) PKA pathways in rat PASMCs.

TMEM16A Regulates Pulmonary Arterial Smooth Muscle Cells Proliferation via p38MAPK/ERK Pathway in High Pulmonary Blood Flow-Induced Pulmonary Arterial Hypertension

2020 ◽  
Vol 58 (1) ◽  
pp. 27-37
Author(s):  
Dongli Liu ◽  
Kai Wang ◽  
Danyan Su ◽  
Yanyun Huang ◽  
Lifeng Shang ◽  
...  
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Vascular Remodeling ◽  
Pulmonary Blood Flow ◽  
Pulmonary Arteries ◽  
Erk Signaling ◽  
Shunt Group ◽  
Pulmonary Arterial ◽  
Arterial Smooth Muscle Cells ◽  
Pulmonary Arterial Smooth Muscle

<b><i>Objective:</i></b> Pulmonary arterial hypertension (PAH) is a complex disease of the small pulmonary arteries that is mainly characterized by vascular remodeling. It has been demonstrated that excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) plays a pivotal role in vascular remodeling during PAH. The present study was undertaken to explore the role of TMEM16A in regulating PASMCs proliferation in high pulmonary blood flow-induced PAH. <b><i>Methods:</i></b> Aortocaval shunt surgery was undertaken to establish an animal model. Pulmonary artery pressure and pulmonary vascular structure remodeling (PVSR) were tested. Immunohistochemical staining and Western blot were performed to investigate the expression of TMEM16A. The proliferation of PASMCs was tested by the MTT assay. After treating PASMCs with TMEM16A-siRNA, the expression of proliferating cell nuclear antigen (PCNA), phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK), and phosphorylated extracellular signal-regulated kinase (p-ERK) signaling in PASMCs were tested. <b><i>Results:</i></b> PAH and PVSR developed 11 weeks postoperation. Elevated expression of TMEM16A accompanied by high expression of PCNA in pulmonary arteries of the shunt group was observed. The increased proliferation of PASMCs and increased expression of TMEM16A and PCNA, along with activated p-p38MAPK and p-ERK signaling in PASMCs of the shunt group, were all attenuated by siRNA-specific TMEM16A knockdown. <b><i>Conclusion:</i></b> TMEM16A regulates PASMCs proliferation in high pulmonary blood flow-induced PAH, and the p38MAPK/ERK signaling pathway is probably involved.

Inhibition of glycolysis by 2-DG increases [Ca2+]i in pulmonary arterial smooth muscle cells

1995 ◽  
Vol 269 (2) ◽  
pp. L203-L208 ◽  
Author(s):  
R. T. Bright ◽  
C. G. Salvaterra ◽  
L. J. Rubin ◽  
X. J. Yuan
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Cyclopiazonic Acid ◽  
Muscle Cells ◽  
Arterial Smooth Muscle ◽  
Inhibition Of Glycolysis ◽  
Pulmonary Arterial ◽  
Arterial Smooth Muscle Cells ◽  
Pulmonary Arterial Smooth Muscle

Inhibition of glycolysis depolarizes single pulmonary arterial smooth muscle cells (PASMC) and potentiates hypoxic pulmonary vasoconstriction (HPV) in isolated perfused rat lungs. Whether glycolytic inhibition causes an increase in the intracellular Ca2+ concentration ([Ca2+]i) in PASMC was determined in this study. [Ca2+]i was measured in primary cultured rat PASMC using the Ca2+ -sensitive fluorescent indicator, fura 2, and quantitative fluorescence microscopy. Extracellular application of the glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), significantly and reversibly increased [Ca2+]i in PASMC. Removal of extracellular Ca2+ and application of the Ca2+ channel blocker, verapamil (10 microM), attenuated, but did not eliminate, the 2-DG-induced rise in [Ca2+]i. In the absence of extracellular Ca2+, however, depletion of inositol triphosphate-sensitive intracellular Ca2+ stores by 10 microM cyclopiazonic acid (CPA) completely abolished the 2-DG-induced increase in [Ca2+]i. The data suggest that 2-DG-induced increases in [Ca2+]i result from both Ca2+ influx through the verapamil-sensitive voltage-gated Ca2+ channels and Ca2+ release from the CPA-sensitive intracellular Ca2+ stores.

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