scholarly journals Endothelium-Independent Hypoxic Contraction Is Prevented Specifically by Nitroglycerin via Inhibition of Akt Kinase in Porcine Coronary Artery

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Huixia Liu ◽  
Yanjing Li ◽  
Yuanming An ◽  
Peixin He ◽  
Liling Wu ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Coronary Arteries ◽  
Rho Kinase ◽  
Underlying Mechanism ◽  
Porcine Coronary Artery ◽  
Sustained Contraction ◽  
Protein Levels ◽  
Hypoxic Vasoconstriction ◽  
Deta Nonoate

Objective. Hypoxia-induced sustained contraction of porcine coronary artery is endothelium-independent and mediated by PI3K/Akt/Rho kinase. Nitroglycerin (NTG) is a vasodilator used to treat angina pectoris and acute heart failure. The present study was to determine the role of NTG in hypoxia-induced endothelium-independent contraction and the underlying mechanism.Methods and Results. Organ chamber technique was used to measure the isometric vessel tension of isolated porcine coronary arteries. Protein levels of phosphorylated and total Akt were determined by western blot. A sustained contraction of porcine coronary arteries induced by hypoxia was significantly reduced by NTG but not by isoproterenol. This contraction was also inhibited by DETA NONOate, 8-Br-cGMP, which can be reversed by ODQ, and Rp-8-Br-PET-cGMPS. The restored contraction was blocked by LY294002. The reduction of Akt-p at Ser-473 by NTG, DETA NONOate, and 8-Br-cGMP was significantly inhibited by ODQ, PKG-I. The decrease in Akt-p level by NTG and 8-Br-cGMP was prevented by calyculin A but not by okadaic acid.Conclusions. These results demonstrated that the endothelium-independent sustained hypoxic vasoconstriction can be prevented by NTG and that the inhibition of PI3K/Akt signaling pathway may be involved.

Constriction to hypoxia-reoxygenation in isolated mouse coronary arteries: role of endothelium and superoxide

1999 ◽  
Vol 87 (4) ◽  
pp. 1392-1396 ◽  
Author(s):  
Qiang Liu
Keyword(s):  
Superoxide Dismutase ◽  
Coronary Artery ◽  
Coronary Arteries ◽  
Flow Condition ◽  
Continuous Measurement ◽  
Video Microscopy ◽  
Hypoxic Vasoconstriction ◽  
Hypoxia Reoxygenation

The aim of the present study was to determine the role of endothelium and superoxide in the responses of isolated mouse coronary arteries to hypoxia-reoxygenation. Isolated mouse coronary artery was cannulated, pressurized at 60 mmHg, and constantly superfused with recirculating Krebs-Ringer bicarbonate solution for continuous measurement of intraluminal diameter (ID) by video microscopy. Under a no-flow condition, hypoxia (0% O2, 30 min) caused vasoconstriction. Reoxygenation caused a further vasoconstriction (ID change from 111.4 ± 11.1 to 91 ± 16.5 μm) that was significantly reduced by removal of endothelium (ID change from 105.4 ± 27 to 109.9 ± 23.4 μm). Cu/Zn superoxide dismutase (150 U/ml) did not alter the hypoxic vasoconstriction but abolished the reoxygenation-caused endothelium-dependent vasoconstriction. Hypoxia-reoxygenation markedly enhanced the generation of superoxide that was significantly reduced by either removing the endothelium or treated these endothelium-intact vessels with superoxide dismutase. These results suggest that, in isolated mouse coronary arteries, hypoxia causes vasoconstriction that is independent of endothelium, whereas reoxygenation causes vasoconstriction that is mediated by enhanced generation of superoxide from endothelium.

Effects of L-arginine analogues on vasomotion of isolated porcine coronary arteries

1995 ◽  
Vol 268 (5) ◽  
pp. H1966-H1972 ◽  
Author(s):  
R. Nakaike ◽  
H. Shimokawa ◽  
H. Yasutake ◽  
H. Sumimoto ◽  
A. Ito ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery ◽  
Coronary Arteries ◽  
Isometric Tension ◽  
Vascular Responses ◽  
Porcine Coronary Artery ◽  
Coronary Vasomotion ◽  
Vasoconstrictor Effect ◽  
Dose Dependent

L-Arginine analogues have been widely used to examine the role of endothelium-derived nitric oxide (NO) in vascular responses; however, the effects of the agents on coronary vasomotion are not fully understood. In this study, we examined the effects of the analogues on vasomotion of isolated porcine coronary arteries. Strips of the porcine coronary artery were suspended for isometric tension recording in Krebs-Henseleit solution. L-Arginine analogues, N omega-nitro-L-arginine methyl ester (L-NAME, 10(-9)-10(-3) M), NG-monomethyl-L-arginine (L-NMMA, 10(-9)-10(-3) M), and NG-nitro-L-arginine (L-NNA, 10(-9)-10(-3) M), caused dose-dependent contractions, which were greater in strips with than in those without endothelium. Those endothelium-dependent contractions were almost abolished by indomethacin (10(-5) M) and FeCl2 (10(-3) M). The latter reduces prostaglandin H2 to 12-heptadecatrienoic acid, which has no vasoconstrictor effect. These results indicate that the L-arginine analogues cause endothelium-dependent contractions that are mediated by prostaglandin endoperoxides and suggest that they have properties other than simple inhibition of NO synthesis in porcine coronary arteries.

Heart failure in an elderly man: where is that coronary?

2021 ◽  
pp. 1-4
Author(s):  
Charlie J. Sang ◽  
Stephen A. Clarkson ◽  
Elizabeth A. Jackson ◽  
Firas Al Solaiman ◽  
Marc G. Cribbs
Keyword(s):  
Heart Failure ◽  
Coronary Artery ◽  
Pulmonary Artery ◽  
Medical Therapy ◽  
Coronary Arteries ◽  
Right Coronary Artery ◽  
Adult Population ◽  
Anomalous Coronary ◽  
Anomalous Coronary Arteries

Abstract Anomalous coronary arteries from the pulmonary artery are uncommon causes of heart failure in the adult population. This case demonstrates the unusual presentation in a patient with anomalous right coronary artery from the pulmonary artery and discusses the complex pathophysiology of this lesion and the role of guideline-directed medical therapy in the management of these patients.

Pertussis toxin-sensitive G proteins in regenerated endothelial cells of porcine coronary artery

1994 ◽  
Vol 267 (3) ◽  
pp. H979-H981 ◽  
Author(s):  
T. Shibano ◽  
J. Codina ◽  
L. Birnbaumer ◽  
P. M. Vanhoutte
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
G Proteins ◽  
Coronary Arteries ◽  
Pertussis Toxin ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
High Cholesterol Diet ◽  
Porcine Coronary Artery ◽  
Yorkshire Pigs

Endothelium-dependent, pertussis toxin-sensitive relaxations are impaired selectively after regeneration of endothelial cells following balloon denudation of the porcine coronary artery. The present study was designed to examine the hypothesis that there is a difference in G proteins modified by pertussis toxin between regenerated and intact endothelial cells. Yorkshire pigs, fed a high-cholesterol diet, underwent balloon denudation of the endothelium of the left anterior descending coronary arteries (LAD). Four weeks after the denudation the animals were killed to detect G proteins by ADP ribosylation catalyzed with pertussis toxin and [32P]NAD, separated on a urea gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In membrane fractions of endothelial cells obtained from previously denuded LAD, G alpha i-1/G alpha i-3 (41 kDa) and G alpha 1-2 (40 kDa) proteins were labeled. The two bands revealed on the gel were the same as those obtained from intact left circumflex coronary arteries (LCX). However, the intensity of the bands was less prominent in the LAD than the LCX. These results suggest that either a decreased amount or a reduced functionality of Gi proteins in the regenerated endothelial cells may account for the impairment in the pertussis toxin-sensitive relaxations after balloon injury of coronary arteries in the pigs.

Two mechanisms mediate relaxation by bradykinin of pig coronary artery: NO-dependent and -independent responses

1991 ◽  
Vol 261 (3) ◽  
pp. H830-H835 ◽  
Author(s):  
C. L. Cowan ◽  
R. A. Cohen
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Coronary Artery ◽  
Thromboxane A2 ◽  
Porcine Coronary Artery ◽  
Cyclic Monophosphate ◽  
Pig Coronary Artery ◽  
Endothelium Dependent Relaxation

The role of nitric oxide and guanosine 3',5'-cyclic monophosphate (cGMP) accumulation in the endothelium-dependent relaxation of the porcine coronary artery to bradykinin was investigated by comparing relaxation and cGMP accumulation in the presence or absence of NG-monomethyl-L-arginine (L-NMMA) and methylene blue. Rings were treated with indomethacin to eliminate the effects of prostaglandins. Relaxation to bradykinin of rings contracted with the thromboxane A2 mimetic U-46619 was not affected by L-NMMA and was only minimally inhibited by methylene blue. Rings contracted with elevated potassium (25 mM) also relaxed completely to bradykinin. However, L-NMMA or methylene blue effectively inhibited relaxation to bradykinin in rings contracted with potassium. cGMP accumulation was stimulated by bradykinin and inhibited by L-NMMA or methylene blue in rings contracted with either U-46619 or potassium. These results suggest that in the absence of nitric oxide-induced cGMP accumulation, a nonprostanoid mechanism exists that is capable of completely relaxing U-46619-contracted coronary artery. This mechanism is either inhibited in or unable to relax potassium-contracted rings. These results also demonstrate that nitric oxide mediates the bradykinin-induced cGMP accumulation that is largely responsible for the relaxation during contraction with potassium.

scholarly journals Relaxation of porcine coronary artery to bradykinin. Role of arachidonic acid.

Hypertension ◽  
1994 ◽  
Vol 23 (6_pt_2) ◽  
pp. 976-981 ◽  
Author(s):  
N L Weintraub ◽  
S N Joshi ◽  
C A Branch ◽  
A H Stephenson ◽  
R S Sprague ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Coronary Artery ◽  
Porcine Coronary Artery

The role of microRNAs in prethrombotic status associated with coronary artery disease

2017 ◽  
Vol 117 (03) ◽  
pp. 429-436 ◽  
Author(s):  
Jie Gao ◽  
Xiaojuan Ma ◽  
Ying Zhang ◽  
Ming Guo ◽  
Dazhuo Shi
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cardiovascular Events ◽  
Thrombus Formation ◽  
Underlying Mechanism ◽  
Fine Tuning ◽  
Diagnostic Biomarkers ◽  
Golden Standard ◽  
Artery Disease

SummaryThe acute cardiovascular events following thrombus formation is a primary cause of morbidity and mortality of patients with coronary artery disease (CAD). Numerous studies have shown that a prethrombotic status, which can be defined as an imbalance between the procoagulant and anticoagulant conditions, would exist for a period of time before thrombogenesis. Therefore, early diagnosis and intervention of prethrombotic status are important for reducing acute cardiovascular events. However, none of prethrombotic indicators have been identified as golden standard for diagnosis of prethrombotic status to date. MicroRNAs (miRNAs), a class of short non-coding RNAs, have been shown to be involved in pathophysiologic processes related to prethrombotic status, such as endothelial dysfunction, platelet activation, impaired fibrinolysis and elevated procoagulant factors, etc. Owing to their multiple and fine-tuning impacts on gene expression, miRNAs raise a novel understanding in the underlying mechanism of prethrombotic status. This review aims to discuss the role of miRNAs in prethrombotic status, especially the differently expressed miRNAs in CAD, which may be meaningful for developing promising diagnostic biomarkers and therapeutic strategies for CAD patients in future.

scholarly journals miR-135b Plays a Neuroprotective Role by Targeting GSK3β in MPP+-Intoxicated SH-SY5Y Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Jianlei Zhang ◽  
Wei Liu ◽  
Yabo Wang ◽  
Shengnan Zhao ◽  
Na Chang
Keyword(s):  
Cell Proliferation ◽  
Glycogen Synthase ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Protective Effects ◽  
Inflammatory Cytokine Production ◽  
Protein Levels

miR-135a-5p was reported to play a crucial role in the protective effects of hydrogen sulfide against Parkinson’s disease (PD) by targeting rho-associated protein kinase 2 (ROCK2). However, the role of another member of miR-135 family (miR-135b) and the underlying mechanism in PD are still unclear. qRT-PCR and western blot showed that miR-135 was downregulated and glycogen synthase kinase 3β (GSK3β) was upregulated at mRNA and protein levels in MPP+-intoxicated SH-SY5Y cells in a dose- and time-dependent manner. MTT, TUNEL, and ELISA assays revealed that miR-135b overexpression significantly promoted cell proliferation and inhibited apoptosis and production of TNF-α and IL-1β in SH-SY5Y cells in the presence of MPP+. Luciferase reporter assay demonstrated that GSK3β was a direct target of miR-135b. Moreover, sodium nitroprusside (SNP), a GSK3β activator, dramatically reversed the effects of miR-135b upregulation on cell proliferation, apoptosis, and inflammatory cytokine production in MPP+-intoxicated SH-SY5Y cells. Taken together, miR-135b exerts a protective role via promotion of proliferation and suppression of apoptosis and neuroinflammation by targeting GSK3β in MPP+-intoxicated SH-SY5Y cells, providing a potential therapeutic target for the treatment of PD.

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