scholarly journals Diphlorethohydroxycarmalol Isolated from Ishige okamurae Exerts Vasodilatory Effects via Calcium Signaling and PI3K/Akt/eNOS Pathway

2021 ◽  
Vol 22 (4) ◽  
pp. 1610 ◽  
Author(s):  
Yu An Lu ◽  
Yunfei Jiang ◽  
Hye-Won Yang ◽  
Jin Hwang ◽  
You-Jin Jeon ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Transgenic Zebrafish ◽  
No Production ◽  
Protective Effects ◽  
In Vivo Experiments ◽  
Vasodilatory Effect ◽  
Ishige Okamurae

Nitric oxide (NO) is released by endothelial cells in the blood vessel wall to enhance vasodilation. Marine polyphenols are known to have protective effects against vascular dysfunction and hypertension. The present study is the first to investigate how diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae affects calcium levels, resulting in enhanced vasodilation. We examined calcium modulation with the well-known receptors, acetylcholine receptor (AchR) and vascular endothelial growth factor 2 (VEGFR2), which are related to NO formation, and further confirmed the vasodilatory effect of DPHC. We confirmed that DPHC stimulated NO production by increasing calcium levels and endothelial nitric oxide synthase (eNOS) expression. DPHC affected AchR and VEGFR2 expression, thereby influencing transient calcium intake. Specific antagonists, atropine and SU5416, were used to verify our findings. Furthermore, based on the results of in vivo experiments, we treated Tg(flk:EGFP) transgenic zebrafish with DPHC to confirm its vasodilatory effect. In conclusion, the present study showed that DPHC modulated calcium transit through AchR and VEGFR2, increasing endothelial-dependent NO production. Thus, DPHC, a natural marine component, can efficiently ameliorate cardiovascular diseases by improving vascular function.

scholarly journals Ecklonia cava Extract and Its Derivative Dieckol Promote Vasodilation by Modulating Calcium Signaling and PI3K/AKT/eNOS Pathway in In Vitro and In Vivo Models

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 438
Author(s):  
Yu-An Lu ◽  
Jun-Geon Je ◽  
Jin Hwang ◽  
You-Jin Jeon ◽  
BoMi Ryu
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Signaling Pathways ◽  
Ecklonia Cava ◽  
Transgenic Zebrafish ◽  
No Production ◽  
Protective Effects ◽  
In Vivo Models ◽  
Vasodilatory Effect

Nitric oxide (NO), an endothelial-derived relaxing factor synthesized by endothelial nitric oxide synthase (eNOS) in endothelial cells, enhances vasodilation by modulating vascular tone. The calcium concentration critically influences eNOS activation in endothelial cells. Thus, modulation of calcium-dependent signaling pathways may be a potential therapeutic strategy to enhance vasodilation. Marine algae reportedly possess protective effects against cardiovascular disorders, including hypertension and vascular dysfunction; however, the underlying molecular signaling pathways remain elusive. In the present study, we extracted and isolated dieckol from Ecklonia cava and investigated calcium transit-enhanced vasodilation. Calcium modulation via the well-known M3 muscarinic acetylcholine receptor (AchM3R), which is linked to NO formation, was investigated and the vasodilatory effect of dieckol was verified. Our results indicated that dieckol effectively promoted NO generation via the PI3K/Akt/eNOS axis and calcium transients influenced by AchM3R. We also treated Tg(flk: EGFP) transgenic zebrafish with dieckol to assess its vasodilatory effect. Dieckol promoted vasodilation by enlarging the dorsal aorta diameter, thus regulating blood flow velocity. In conclusion, our findings suggest that dieckol modulates calcium transit through AchM3R, increases endothelial-dependent NO production, and efficiently enhances vasodilation. Thus, E. cava and its derivative, dieckol, can be considered as potential natural vasodilators.

Preventive and therapeutic effects of quercetin on lipopolysaccharide-induced oxidative stress and vascular dysfunction in mice

2012 ◽  
Vol 90 (10) ◽  
pp. 1345-1353 ◽  
Author(s):  
Upa Kukongviriyapan ◽  
Kwanjit Sompamit ◽  
Patchareewan Pannangpetch ◽  
Veerapol Kukongviriyapan ◽  
Wanida Donpunha
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Redox Status ◽  
Protein Carbonyl ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Vascular Responsiveness

Quercetin, a dietary antioxidant flavonoid, possesses strong anti-inflammatory and cytoprotective activities. The effects were investigated in an animal model of lipopolysaccharide (LPS)-induced endotoxaemia and vascular dysfunction in vivo. Male ICR mice were injected with LPS (10 mg/kg; i.p.). Quercetin (50 or 100 mg/kg) was intragastrically administered either before or after LPS administration. Fifteen hours after LPS injection, mice were found in endotoxaemic condition, as manifested by hypotension, tachycardia, and blunted vascular responses to vasodilators and vasoconstrictor. The symptoms were accompanied by increased aortic iNOS protein expression, decreased aortic eNOS protein expression, marked suppression of cellular glutathione (GSH) redox status, enhanced aortic superoxide production, increased plasma malodialdehyde and protein carbonyl, and elevated urinary nitrate/nitrite. Treatment with quercetin either before or after LPS preserved the vascular function, as blood pressure, heart rate, vascular responsiveness were restored to near normal values, particularly when quercetin was given as a preventive regimen. The vascular protective effects were associated with upregulation of eNOS expression, reduction of oxidative stress, and maintained blood GSH redox ratio. Overall findings suggest the beneficial effect of quercetin on the prevention and restoration of a failing eNOS system and alleviation of oxidative stress and vascular dysfunction against endotoxin-induced shock in mice.

scholarly journals The role of tetrahydrobiopterin in inflammation and cardiovascular disease

2012 ◽  
Vol 108 (11) ◽  
pp. 832-839 ◽  
Author(s):  
Eileen McNeill ◽  
Keith Channon
Keyword(s):  
Nitric Oxide ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Cell Types ◽  
No Production ◽  
Major Site ◽  
Cellular Redox ◽  
Oxide Synthase ◽  
New Evidence

SummaryThe cofactor tetrahydrobiopterin (BH4) is required for nitric oxide (NO) production by all nitric oxide synthase (NOS) enzymes and is a key regulator of cellular redox signalling. When BH4 levels become limiting NOS enzymes become ‘uncoupled’ and produce superoxide rather than NO. Endothelial cell BH4 is required for the maintenance of vascular function through NO production, and reduced BH4 levels are associated with vascular dysfunction. Evidence increasingly points to important roles for BH4 and NOS enzymes in other vascular cell types. Leukocytes have a fundamental role in atherosclerosis, and new evidence points to a role in the control of hypertension. Leukocytes are a major site of iNOS expression, and the regulation of this isoform is another mechanism by which BH4 availability may modulate disease. This review provides an overview of BH4 control of NOS function in both endothelial cells and leukocytes in the context of vascular disease and current therapeutic evaluations.

scholarly journals Matrix Metalloproteinases and Arterial Hypertension: Role of Oxidative Stress and Nitric Oxide in Vascular Functional and Structural Alterations

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 585
Author(s):  
Alejandro F. Prado ◽  
Rose I. M. Batista ◽  
Jose E. Tanus-Santos ◽  
Raquel F. Gerlach
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Extracellular Matrix ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Protective Effects ◽  
Pathophysiological Mechanisms ◽  
Emerging Therapies ◽  
Extracellular Matrix Components ◽  
Matrix Components

Various pathophysiological mechanisms have been implicated in hypertension, but those resulting in vascular dysfunction and remodeling are critical and may help to identify critical pharmacological targets. This mini-review article focuses on central mechanisms contributing to the vascular dysfunction and remodeling of hypertension, increased oxidative stress and impaired nitric oxide (NO) bioavailability, which enhance vascular matrix metalloproteinase (MMP) activity. The relationship between NO, MMP and oxidative stress culminating in the vascular alterations of hypertension is examined. While the alterations of hypertension are not fully attributable to these pathophysiological mechanisms, there is strong evidence that such mechanisms play critical roles in increasing vascular MMP expression and activity, thus resulting in abnormal degradation of extracellular matrix components, receptors, peptides, and intracellular proteins involved in the regulation of vascular function and structure. Imbalanced vascular MMP activity promotes vasoconstriction and impairs vasodilation, stimulating vascular smooth muscle cells (VSMC) to switch from contractile to synthetic phenotypes, thus facilitating cell growth or migration, which is associated with the deposition of extracellular matrix components. Finally, the protective effects of MMP inhibitors, antioxidants and drugs that enhance vascular NO activity are briefly discussed. Newly emerging therapies that address these essential mechanisms may offer significant advantages to prevent vascular remodeling in hypertensive patients.

In vivo stimulatory effect of erythropoietin on endothelial nitric oxide synthase in cerebral arteries

2006 ◽  
Vol 291 (2) ◽  
pp. H781-H786 ◽  
Author(s):  
Anantha Vijay R. Santhanam ◽  
Leslie A. Smith ◽  
Karl A. Nath ◽  
Zvonimir S. Katusic
Keyword(s):  
Nitric Oxide ◽  
Cerebral Arteries ◽  
No Production ◽  
Protective Effects ◽  
Vascular Protection ◽  
Vascular Effects ◽  
No Donor ◽  
Vasomotor Function ◽  
Basilar Arteries

The discovery of tissue protective effects of erythropoietin has stimulated significant interest in erythropoietin (Epo) as a novel therapeutic approach to vascular protection. The present study was designed to determine the cerebral vascular effects of recombinant Epo in vivo. Recombinant adenoviral vectors (109 plaque-forming units/animal) encoding genes for human erythropoietin (AdEpo) and β-galactosidase (AdLacZ) were injected into the cisterna magna of rabbits. After 48 h, basilar arteries were harvested for analysis of vasomotor function, Western blotting, and measurement of cGMP levels. Gene transfer of AdEpo increased the expressions of recombinant Epo and its receptor in the basilar arteries. Arteries exposed to recombinant Epo demonstrated attenuation of contractile responses to histamine (10−9 to 10−5 mol/l) ( P < 0.05, n = 5). Endothelium-dependent relaxations to acetylcholine (10−9 to 10−5 mol/l) were significantly augmented ( P < 0.05, n = 5), whereas endothelium-independent relaxations to a nitric oxide (NO) donor 2-( N, N-diethylamino)diazenolate-2-oxide sodium salt remained unchanged in AdEpo-transduced basilar arteries. Transduction with AdEpo increased the protein expression of endothelial NO synthase (eNOS) and phosphorylated the S1177 form of the enzyme. Basal levels of cGMP were significantly elevated in arteries transduced with AdEpo consistent with increased NO production. Our studies suggest that in cerebral circulation, Epo enhances endothelium-dependent vasodilatation mediated by NO. This effect could play an important role in the vascular protective effect of Epo.

Abstract 1138: Endogenous Adipocyte-Derived Factors Diminish Coronary Endothelial-Dependent Vasodilation Via Inhibition Of Nitric Oxide Synthase

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Gregory A Payne ◽  
Lena Borbouse ◽  
Gregory M Dick ◽  
Johnathan D Tune
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Coronary Blood Flow ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Dependent Manner ◽  
Pericardial Adipose Tissue ◽  
Oxide Synthase

Adipocytokines may be the molecular link between obesity and vascular disease; however, effects of these factors on coronary vascular function have not been delineated. Accordingly, this study was designed to examine mechanisms by which endogenous adipocyte-derived factors impair coronary endothelial-dependent vasodilation in vivo . Experiments were conducted in open-chest anesthetized dogs (n = 16) before and during treatment with endogenous adipocyte-derived factors. Phosphate buffered saline was conditioned in a shaking water bath with parietal pericardial adipose tissue (3 g/ml) for 30 min at 37°C. The conditioned buffer was then filtered (0.2 μm) and infused directly into the coronary circulation (0.3 ml/min). Conditioned buffer did not significantly affect baseline coronary blood flow (0.50 ± 0.01 vs. 0.61 ± 0.05 ml/min/g, p = 0.68), mean arterial pressure (103 ± 6 vs. 96 ± 9 mmHg, p = 0.74), or heart rate (87 ± 13 vs. 110 ± 24 beats/min, p = 0.44). Conditioned buffer had no effect on responses to intracoronary angiotensin II (2.5 – 750 ng; 74 vs. 70% vasoconstriction). Under control conditions, bradykinin (0.03 – 3 μg/min) increased coronary blood flow (303 ± 65%) to 2.02 ± 0.31 ml/min/g in a dose-dependent manner. Conditioned buffer attenuated maximum bradykinin vasodilation to 1.64 ± 0.26 ml/min/g (167 ± 33% increase; p < 0.05). This decrease in endothelial-dependent dilation was not due to increases in superoxide production, as administration of the superoxide dismutase mimetic Tempol (10 mg/min, ic) did not improve bradykinin vasodilation (120 ± 27% increase; p < 0.05). Inhibition of nitric oxide synthase with L-NAME (150 μg/min, ic) reduced maximum bradykinin vasodilation to 0.93 ± 0.04 ml/min/g (p < 0.05) and endogenous adipocyte-derived factors had no further inhibitory effect (0.82 ± 0.09 ml/min/g, p = 0.24). These data indicate that endogenous adipocyte-derived factors diminish endothelial-dependent coronary vasodilation via inhibition of nitric oxide synthase rather than a reduction in nitric oxide bioavailability by superoxide. Our findings importantly link endogenous adipocyte-derived factors with pro-atherogenic coronary vascular dysfunction in vivo .

scholarly journals Abnormal nitric oxide production in aged rat mesenteric arteries is mediated by NAD(P)H oxidase-derived peroxide

2009 ◽  
Vol 297 (6) ◽  
pp. H2227-H2233 ◽  
Author(s):  
Xiaosun Zhou ◽  
H. Glenn Bohlen ◽  
Joseph L. Unthank ◽  
Steven J. Miller
Keyword(s):  
Nitric Oxide ◽  
Vascular Function ◽  
Spontaneously Hypertensive Rat ◽  
Oxidant Stress ◽  
Mesenteric Arteries ◽  
No Production ◽  
Aged Rats ◽  
Wistar Kyoto Rats ◽  
Wistar Kyoto

Previous work in our laboratory showed increased basal periarterial nitric oxide (NO) and H2O2 concentrations in the spontaneously hypertensive rat, characterized by oxidant stress, as well as impaired flow-mediated NO production that was corrected by a reduction of periarterial H2O2. Aging is also associated with an increase in vascular reactive oxygen species and results in abnormal vascular function. The current study was designed to assess the role of H2O2 in regulating NO production during vascular aging. In vivo, real-time NO and H2O2 concentrations were measured by microelectrodes in mesenteric arteries of retired breeder (aged; 8–12 mo) and young (2 to 3 mo) Wistar-Kyoto rats under conditions of altered flow. The results in aged rats revealed elevated basal NO (1,611 ± 286 vs. 793 ± 112 nM, P < 0.05) and H2O2 concentrations (16 ± 2 vs. 9 ± 1 μM, P < 0.05) and a flow-mediated increase in H2O2 but not NO production. Pretreatment of aged rats with the antioxidant apocynin lowered both basal H2O2 (8 ± 1 μM) and NO (760 ± 102 nM) to young levels and restored flow-mediated NO production. Similar results were obtained with the NAD(P)H oxidase inhibitor gp91ds-tat. In addition, acute incubation with topical polyethylene-glycolated catalase lowered the baseline NO concentration and restored flow-mediated NO production. Taken together, the data indicate that elevated baseline and suppressed flow-mediated NO production in aged Wistar-Kyoto rats are mediated by NAD(P)H oxidase-derived H2O2.

scholarly journals Vascular Dysfunction in Malaria: Understanding the Role of the Endothelial Glycocalyx

2021 ◽  
Vol 9 ◽  
Author(s):  
Margaret A. Bush ◽  
Nicholas M. Anstey ◽  
Tsin W. Yeo ◽  
Salvatore M. Florence ◽  
Donald L. Granger ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Blood Perfusion ◽  
Endothelial Activation ◽  
Cellular Adhesion ◽  
Adverse Outcomes ◽  
Endothelial Glycocalyx ◽  
Nitric Oxide Signaling

Malaria caused by Plasmodium falciparum results in over 400,000 deaths annually, predominantly affecting African children. In addition, non-falciparum species including vivax and knowlesi cause significant morbidity and mortality. Vascular dysfunction is a key feature in malaria pathogenesis leading to impaired blood perfusion, vascular obstruction, and tissue hypoxia. Contributing factors include adhesion of infected RBC to endothelium, endothelial activation, and reduced nitric oxide formation. Endothelial glycocalyx (eGC) protects the vasculature by maintaining vessel integrity and regulating cellular adhesion and nitric oxide signaling pathways. Breakdown of eGC is known to occur in infectious diseases such as bacterial sepsis and dengue and is associated with adverse outcomes. Emerging studies using biochemical markers and in vivo imaging suggest that eGC breakdown occurs during Plasmodium infection and is associated with markers of malaria disease severity, endothelial activation, and vascular function. In this review, we describe characteristics of eGC breakdown in malaria and discuss how these relate to vascular dysfunction and adverse outcomes. Further understanding of this process may lead to adjunctive therapy to preserve or restore damaged eGC and reduce microvascular dysfunction and the morbidity/mortality of malaria.

scholarly journals Samchulkunbi-Tang Alleviates Vascular Endothelial Disorder and Renal Dysfunction in Nitric Oxide-Deficient Hypertensive Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Mi Hyeon Hong ◽  
Jin Seok Hwang ◽  
Byung Hyuk Han ◽  
Yun Jung Lee ◽  
Jung Joo Yoon ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ming Dynasty ◽  
Vascular Function ◽  
Gastric Ulcers ◽  
Human Umbilical Cord ◽  
No Production ◽  
Protective Effects ◽  
Hypertensive Rats ◽  
Enos Expression ◽  
Hypertensive Rat

Samchulkunbi-tang (SCT, Shen Zhu Jian pi tang in Chinese) is said to have been first recorded by Zheng Zhi Zhun Sheng during the Ming Dynasty in China. Records of SCT in Korea are known to have been cited in Donguibogam (Dong Yi Bao Jian in Chinese), Uibang Hwaltu (Yi Fang Huo Tao in Chinese), and Bang Yak Hapyeon (Fang Yao He Bian in China). Although SCT is widely used in treating chronic gastritis and gastric ulcers, the beneficial effect on renal vascular function is unknown. Hypertension is a risk factor for cardiovascular disease and endothelial dysfunction in humans and experimental animal models of arterial hypertension. In addition, kidney dysfunction is characterized by hypertension diseases. This study was conducted to evaluate the effect of SCT on the vascular function in vitro (human umbilical cord endothelial cells, HUVECs) and in vivo (NG‐nitro‐L‐arginine methyl ester, L-NAME-induced hypertensive rats). The phosphorylation of protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) is closely related to nitric oxide (NO) production in HUVECs, and SCT in this study significantly increased these. For three weeks, hypertensive rat models were induced by L-NAME administration (40 mg/kg/day) with portable water. It was followed by oral administration with 100 and 200 mg/kg/day for two weeks to confirm the effectiveness of SCT. As a result, systolic blood pressure decreased in the SCT-treated groups, compared with that in the L-NAME-induced hypertensive group. SCT treatment restored vasorelaxation by stimulating acetylcholine and cGMP production in the thoracic aorta. In addition, SCT treatment decreased intima-media thickness, attenuated the reduction of eNOS expression, and increased endothelin-1 expression. It also increased p-Akt and p-eNOS expression in hypertensive rat aorta. Furthermore, regarding renal function parameters, SCT ameliorated urine osmolality, urine albumin level, serum creatinine, and blood urea nitrogen levels. These results demonstrate that the oriental medicine SCT exerts potent vascular and renal protective effects on nitric oxide-deficient hypertensive rats and HUVECs

scholarly journals The Inhibitory Effect of Ojeoksan on Early and Advanced Atherosclerosis

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1256 ◽  
Author(s):  
Byung Han ◽  
Chang Seo ◽  
Jung Yoon ◽  
Hye Kim ◽  
You Ahn ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Dysfunction ◽  
Umbilical Vein ◽  
Vascular Inflammation ◽  
Inhibitory Effect ◽  
Western Diet ◽  
No Production ◽  
Necrosis Factor Alpha

Atherosclerosis is closely related to vascular dysfunction and hypertension. Ojeoksan (OJS), originally recorded in an ancient Korean medicinal book named “Donguibogam”, is a well-known, blended herbal formula. This study was carried out to investigate the beneficial effects of OJS on atherosclerosis in vitro and in vivo. Western-diet-fed apolipoprotein-E gene-deficient mice (ApoE −/−) were used for this study for 16 weeks, and their vascular dysfunction and inflammation were analyzed. OJS-treated ApoE −/− mice showed lowered blood pressure and glucose levels. The levels of metabolic parameters with hyperlipidemia attenuated following OJS administration. Hematoxylin and eosin (H&E) staining revealed that treatment with OJS reduced atherosclerotic lesions. OJS also suppressed the expression of adhesion molecules and matrix metalloproteinases (MMPs) compared to Western-diet-fed ApoE −/− mice and tumor necrosis factor-alpha (TNF-α)-stimulated human umbilical vein endothelial cells (HUVECs). Expression levels of MicroRNAs (miRNA)-10a, -126 3p were increased in OJS-fed ApoE −/− mice. OJS significantly increased the phosphorylation of endothelial nitric oxide synthase (eNOS) and protein kinase B (Akt), which are involved in nitric oxide (NO) production. OJS also regulated eNOS coupling by increasing the expression of endothelial GTP Cyclohydrolase-1 (GTPCH). Taken together, OJS has a protective effect on vascular inflammation via eNOS coupling-mediated NO production and might be a potential therapeutic agent for both early and advanced atherosclerosis.

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