scholarly journals Phasic contractions of rat mesenteric lymphatics increase basal and phasic nitric oxide generation in vivo

2009 ◽  
Vol 297 (4) ◽  
pp. H1319-H1328 ◽  
Author(s):  
H. Glenn Bohlen ◽  
Wei Wang ◽  
Anatoliy Gashev ◽  
Olga Gasheva ◽  
Dave Zawieja
Keyword(s):  
Nitric Oxide ◽  
Relaxation Mechanism ◽  
Lymph Flow ◽  
Lymphatic Endothelium ◽  
Contraction Frequency ◽  
Diastolic Relaxation ◽  
Intravenous Saline ◽  
First Time

Multiple investigators have shown interdependence of lymphatic contractions on nitric oxide (NO) activity by pharmacological and traumatic suppression of endothelial NO synthase (eNOS). We demonstrated that lymphatic diastolic relaxation is particularly sensitive to NO from the lymphatic endothelium. The predicted mechanism is shear forces produced by the lymph flow during phasic pumping, activating eNOS in the lymphatic endothelium to produce NO. We measured [NO] during phasic contractions using microelectrodes on in situ mesenteric lymphatics in anesthetized rats under basal conditions and with an intravenous saline bolus (0.5 ml/100 g) or infusion (0.5 ml·100 g−1·h−1). Under basal conditions, [NO] measured on the tubular portions of the lymphatics was ∼200–250 nM, slightly higher than in the adjacent adipocyte microvasculature, whereas [NO] measured on the lymphatic bulb surface was ∼400 nM. Immunohistochemistry of eNOS in isolated lympathics indicated a much greater expression in the lymph valves and surrounding bulb area than in the tubular regions. During phasic lymphatic contractions, the valve and tubular [NO] increased with each contraction, and during intravenous saline infusion, [NO] increased in proportion to the contraction frequency and, presumably, lymph flow. The partial blockade of eNOS over ∼1 cm length with Nω-nitro-l-arginine methyl ester lowered the [NO]. These in vivo data document for the first time that both valvular and tubular lymphatic segments increase NO generation during each phasic contraction and that [NO] summated with increased contraction frequency. The combined data predict regional variations in eNOS and [NO] in the tubular and valve areas, plus the summated NO responses dependent on contraction frequency provide for a complex relaxation mechanism involving NO.

Increasing dihydrobiopterin causes dysfunction of endothelial nitric oxide synthase in rats in vivo

2011 ◽  
Vol 301 (3) ◽  
pp. H721-H729 ◽  
Author(s):  
Katsuhiko Noguchi ◽  
Naobumi Hamadate ◽  
Toshihiro Matsuzaki ◽  
Mayuko Sakanashi ◽  
Junko Nakasone ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Control Treatment ◽  
Enos Uncoupling ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
First Time

An elevation of oxidized forms of tetrahydrobiopterin (BH4), especially dihydrobiopterin (BH2), has been reported in the setting of oxidative stress, such as arteriosclerotic/atherosclerotic disorders, where endothelial nitric oxide synthase (eNOS) is dysfunctional, but the role of BH2 in the regulation of eNOS activity in vivo remains to be evaluated. This study was designed to clarify whether increasing BH2 concentration causes endothelial dysfunction in rats. To increase vascular BH2 levels, the BH2 precursor sepiapterin (SEP) was intravenously given after the administration of the specific dihydrofolate reductase inhibitor methotrexate (MTX) to block intracellular conversion of BH2 to BH4. MTX/SEP treatment did not significantly affect aortic BH4 levels compared with control treatment. However, MTX/SEP treatment markedly augmented aortic BH2 levels (291.1 ± 29.2 vs. 33.4 ± 6.4 pmol/g, P < 0.01) in association with moderate hypertension. Treatment with MTX alone did not significantly alter blood pressure or BH4 levels but decreased the BH4-to-BH2 ratio. Treatment with MTX/SEP, but not with MTX alone, impaired ACh-induced vasodilator and depressor responses compared with the control treatment (both P < 0.05) and also aggravated ACh-induced endothelium-dependent relaxations ( P < 0.05) of isolated aortas without affecting sodium nitroprusside-induced endothelium-independent relaxations. Importantly, MTX/SEP treatment significantly enhanced aortic superoxide production, which was diminished by NOS inhibitor treatment, and the impaired ACh-induced relaxations were reversed with SOD ( P < 0.05), suggesting the involvement of eNOS uncoupling. These results indicate, for the first time, that increasing BH2 causes eNOS dysfunction in vivo even in the absence of BH4 deficiency, demonstrating a novel insight into the regulation of endothelial function.

Abstract 18060: TRAIL Promotes Angiogenesis and Ischemia-Induced Neovascularisation via NOX4, H2O2 and Nitric Oxide-Dependent Mechanisms

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Belinda A Di Bartolo ◽  
Sian P Cartland ◽  
Leonel Prado-Lourenco ◽  
Nor Saadah M Azahri ◽  
Thuan Thai ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiogenic Factor ◽  
Tubule Formation ◽  
Nitric Oxide Synthase Inhibitor ◽  
Therapeutic Implications ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
First Time

Background: Angiogenesis and neovascularization are essential processes that follow ischemia insults. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) not only induces endothelial cell (EC) death and inhibits angiogenesis, but also promotes EC migration, invasion and proliferation in vitro . These seemingly opposite effects make its role in angiogenesis in vivo unclear. Using TRAIL -/- and wild-type mice, we sought to determine the role of TRAIL in angiogenesis and neovascularisation. We also sought mechanisms in vitro . Methods and Results: Reduced vascularisation assessed by real-time in vivo 3D Vevo ultrasound imaging and CD31 staining was observed in TRAIL -/- mice 28 d after hindlimb ischemia. Moreover, reduced capillary formation and increased apoptosis was evident in TRAIL -/- muscles even at 3 d after ischemic surgery. We have previously shown that fibroblast growth factor-2 (FGF-2), a potent angiogenic factor, regulates TRAIL gene expression in vascular smooth muscle cells. Indeed, FGF-2 also regulates TRAIL expression in ECs, and FGF-2-inducible proliferation, migration and tubule formation was inhibited with siRNA targeting TRAIL. Notably, both FGF-2 and TRAIL significantly increased NOX4 expression. TRAIL-inducible angiogenic activity in ECs was inhibited with siRNAs targeting NOX4, and consistent with these, NOX4 mRNA was reduced in 3 d ischemic hindlimbs of TRAIL -/- mice. TRAIL stimulated intracellular H 2 O 2 levels in ECs, and TRAIL-inducible proliferation, migration and tubule formation was inhibited with not only PEG-catalase, a H 2 O 2 scavenger, but also blocked with L-NAME, a nitric oxide synthase inhibitor. Conclusions: This is the first demonstration showing that TRAIL promotes angiogenesis in vivo . We show for the first time that the TRAIL stimulates NOX4 expression to mediate nitric oxide-dependent angiogenic effects. This has significant therapeutic implications such that TRAIL may improve the angiogenic response to ischemia and increase perfusion recovery in patients with CVD and diabetes.

scholarly journals INTEGRINS MEDIATE PLACENTAL EXTRACELLULAR VESICLE TRAFFICKING TO LUNG AND LIVER IN VIVO

2020 ◽  
Author(s):  
Sean L. Nguyen ◽  
Soo Hyun Ahn ◽  
Jacob W. Greenberg ◽  
Benjamin W. Collaer ◽  
Dalen W. Agnew ◽  
...  
Keyword(s):  
Immune Cells ◽  
Extracellular Vesicle ◽  
Dependent Manner ◽  
Cellular Phenotype ◽  
Reporter Mouse ◽  
Membrane Bound ◽  
First Time

ABSTRACTMembrane-bound extracellular vesicles (EVs) mediate intercellular communication in all organisms, and those produced by placental mammals have become increasingly recognized as significant mediators of fetal-maternal communication. Here, we aimed to identify maternal cells targeted by placental EVs and elucidate the mechanisms by which they traffic to these cells. Exogenously administered pregnancy-associated EVs traffic specifically to the lung; further, placental EVs associate with lung interstitial macrophages and liver Kupffer cells in an integrin-dependent manner. Localization of EV to maternal lungs was confirmed in unmanipulated pregnancy using a transgenic reporter mouse model, which also provided in situ and in vitro evidence that fetally-derived EVs, rarely, may cause genetic alteration of maternal cells. These results provide for the first time direct in vivo evidence for targeting of placental EVs to maternal immune cells, and further, evidence that EVs can alter cellular phenotype.

Acute Exposure of Collecting Lymphatic Vessels to Low-Density Lipoproteins Increases Both Contraction Frequency and Lymph Flow: An In Vivo Mechanical Insight

2020 ◽  
Vol 18 (2) ◽  
pp. 146-155 ◽  
Author(s):  
Eleonora Solari ◽  
Cristiana Marcozzi ◽  
Barbara Bartolini ◽  
Manuela Viola ◽  
Daniela Negrini ◽  
...  
Keyword(s):  
Lymphatic Vessels ◽  
Low Density Lipoproteins ◽  
Lymph Flow ◽  
Acute Exposure ◽  
Low Density ◽  
Contraction Frequency

scholarly journals Astrovirus-Induced Synthesis of Nitric Oxide Contributes to Virus Control during Infection

2004 ◽  
Vol 78 (3) ◽  
pp. 1564-1574 ◽  
Author(s):  
Matthew D. Koci ◽  
Laura A. Kelley ◽  
Diane Larsen ◽  
Stacey Schultz-Cherry
Keyword(s):  
Nitric Oxide ◽  
Ex Vivo ◽  
Small Animal ◽  
Innate Immune Responses ◽  
Vitro Analysis ◽  
Oxide Synthase ◽  
First Time

ABSTRACT Astrovirus is one of the major causes of infant and childhood diarrhea worldwide. Our understanding of astrovirus pathogenesis trails behind our knowledge of its molecular and epidemiologic properties. Using a recently developed small-animal model, we investigated the mechanisms by which astrovirus induces diarrhea and the role of both the adaptive and innate immune responses to turkey astrovirus type-2 (TAstV-2) infection. Astrovirus-infected animals were analyzed for changes in total lymphocyte populations, alterations in CD4+/CD8+ ratios, production of virus-specific antibodies (Abs), and macrophage activation. There were no changes in the numbers of circulating or splenic lymphocytes or in CD4+/CD8+ ratios compared to controls. Additionally, there was only a modest production of virus-specific Abs. However, adherent spleen cells from infected animals produced more nitric oxide (NO) in response to ex vivo stimulation with lipopolysaccharide. In vitro analysis demonstrated that TAstV-2 induced macrophage production of inducible nitric oxide synthase. Studies using NO donors and inhibitors in vivo demonstrated, for the first time, that NO inhibited astrovirus replication. These studies suggest that NO is important in limiting astrovirus replication and are the first, to our knowledge, to describe the potential role of innate immunity in astrovirus infection.

Organic semiconducting nanoprobe with redox-activatable NIR-II fluorescence forin vivoreal-time monitoring of drug toxicity

2019 ◽  
Vol 55 (1) ◽  
pp. 27-30 ◽  
Author(s):  
Yufu Tang ◽  
Yuanyuan Li ◽  
Zhen Wang ◽  
Feng Pei ◽  
Xiaoming Hu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Real Time ◽  
Drug Toxicity ◽  
Drug Dose ◽  
Non Invasive ◽  
Dose Dependent

A nitric-oxide-activatable organic semiconducting nanoprobe was developed forin vivo,in situ, real-time and non-invasive NIR-II fluorescence monitoring of drug-dose-dependent hepatotoxicity.

scholarly journals Fiber-integrated Brillouin microspectroscopy: Towards Brillouin endoscopy

2017 ◽  
Vol 10 (06) ◽  
pp. 1742002 ◽  
Author(s):  
Irina V. Kabakova ◽  
YuChen Xiang ◽  
Carl Paterson ◽  
Peter Török
Keyword(s):  
Optical Fiber ◽  
Brillouin Scattering ◽  
Region Of Interest ◽  
The Body ◽  
Propagation Model ◽  
Micromechanical Characterization ◽  
First Time

Brillouin imaging (BI) for micromechanical characterization of tissues and biomaterials is a fast-developing field of research with a strong potential for medical diagnosis of disease-modified tissues and cells. Although the principles of BI imply its compatibility with in vivo and in situ measurements, the integration of BI with a flexible catheter, capable of reaching the region of interest within the body, is yet to be reported. Here, for the first time, we experimentally investigate integration of the Brillouin spectroscope with standard optical fiber components to achieve a Brillouin endoscope. The performance of single-fiber and dual-fiber endoscopes are demonstrated and analyzed. We show that a major challenge in construction of Brillouin endoscopes is the strong backward Brillouin scattering in the optical fiber and we present a dual-fiber geometry as a possible solution. Measurements of Brillouin spectra in test liquids (water, ethanol and glycerol) are demonstrated using the dual-fiber endoscope and its performance is analyzed numerically with the help of a beam propagation model.

scholarly journals Nitric oxide rapidly scavenges tyrosine and tryptophan radicals

1995 ◽  
Vol 310 (3) ◽  
pp. 745-749 ◽  
Author(s):  
J P Eiserich ◽  
J Butler ◽  
A van der Vliet ◽  
C E Cross ◽  
B Halliwell
Keyword(s):  
Nitric Oxide ◽  
Biologically Relevant ◽  
Tyrosine Residues ◽  
Transfer Processes ◽  
Diffusion Controlled ◽  
Electron Transfer Processes ◽  
Protein Radicals ◽  
First Time

By utilizing a pulse-radiolytic technique, we demonstrate for the first time that the rate constant for the reaction of nitric oxide (.NO) with biologically relevant tyrosine and tryptophan radicals (Tyr. and Trp. respectively) in amino acids, peptides and proteins is of the order of (1-2) x 10(9) M-1.s-1. We also show that .NO effectively interferes with electron-transfer processes between tryptophan and tyrosine residues in proteins subjected to pulse radiolysis. The near diffusion-controlled rates of these reactions, coupled with the increasingly recognized role of protein radicals in enzyme catalysis and oxidative damage, suggest that Tyr. and Trp. are likely and important targets for .NO generated in vivo.

scholarly journals Mesenteric lymph flow in adult and aged rats

2011 ◽  
Vol 301 (5) ◽  
pp. H1828-H1840 ◽  
Author(s):  
Tony J. Akl ◽  
Takashi Nagai ◽  
Gerard L. Coté ◽  
Anatoliy A. Gashev
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Ex Vivo ◽  
Lymphatic Vessels ◽  
Lymph Flow ◽  
Contraction Frequency ◽  
Stress Load ◽  
Wall Shear ◽  
Contractile Characteristics

The objective of study was to evaluate the aging-associated changes, contractile characteristics of mesenteric lymphatic vessels (MLV), and lymph flow in vivo in male 9- and 24-mo-old Fischer-344 rats. Lymphatic diameter, contraction amplitude, contraction frequency, and fractional pump flow, lymph flow velocity, wall shear stress, and minute active wall shear stress load were determined in MLV in vivo before and after Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME) application at 100 μM. The active pumping of the aged rat MLV in vivo was found to be severely depleted, predominantly through the aging-associated decrease in lymphatic contractile frequency. Such changes correlate with enlargement of aged MLV, which experienced much lower minute active shear stress load than adult vessels. At the same time, pumping in aged MLV in vivo may be rapidly increased back to levels of adult vessels predominantly through the increase in contraction frequency induced by nitric oxide (NO) elimination. Findings support the idea that in aged tissues surrounding the aged MLV, the additional source of some yet unlinked lymphatic contraction-stimulatory metabolites is counterbalanced or blocked by NO release. The comparative analysis of the control data obtained from experiments with both adult and aged MLV in vivo and from isolated vessel-based studies clearly demonstrated that ex vivo isolated lymphatic vessels exhibit identical contractile characteristics to lymphatic vessels in vivo.

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