Induced Nitric Oxide Impairs Relaxation but Not Contraction in Endotoxin-Exposed Rat Pulmonary Arteries

Boer, Christa; Groeneveld, A. B. Johan; Scheffer, Gert Jan; Lange, J. de; Westerhof, Nico; Sipkema, Pieter

doi:10.1016/j.jss.2005.03.015

Cited by 10 publications

(6 citation statements)

References 30 publications

(50 reference statements)

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“…On the other hand, De Mey and colleagues did not observe any changes in responses to high K + solution in renal arteries cultured in serum‐supplemented media . Exposure to LPS significantly attenuated carbachol‐induced vasodilation, indicating impaired endothelial function, in agreement with previous studies in various vessel specimens . Impaired responses to muscarinic receptor agonists could also be explained by loss of receptors or changes in downstream signalling such as eNOS .…”

Section: Discussionsupporting

confidence: 90%

Lipopolysaccharides, but not Angiotensin ll, lnduces Direct Pro‐lnflammatory Effects in Cultured Mouse Arteries and Human Endothelial and Vascular Smooth Muscle Cells

Outzen

Zaki

Mehryar

et al. 2017

Basic Clin Pharma Tox

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Angiotensin II (Ang II) might induce pro-inflammatory effects directly in the vascular wall independently of its haemodynamic effects. The aim of our study was to investigate the putative direct pro-inflammatory and vasomotor effects of Ang II and compare to those of lipopolysaccharides (LPS) in mouse isolated mesenteric resistance-sized arteries (MRA) supported by experiments in cultured human primary endothelial and vascular smooth muscle cells. Results showed that 24-hr organ culture of mouse MRA with 10 nM Ang II had, unlike 100 ng/mL LPS, no effects on IL-6 or MCP-1 secretion, VCAM1 mRNA expression or endothelial function, while Ang II significantly decreased maximal vasomotor responses to phenylephrine. In support, 24-hr organ culture of mouse MRA significantly suppressed Agtr1a mRNA and augmented Tlr4 mRNA along with attenuated vasomotor responses to Ang II. Moreover, contrary to LPS and TNF-α, Ang II and [Sar1]-Ang II had no concentration- or time-dependent effects on IL-6 and MCP-1 secretion in human umbilical vein endothelial cells (HUVEC) and human aortic smooth muscle cells (HASMC). AGTR1 or AGTR2 mRNA expression was undetectable in HUVEC, whereas HASMC expressed only AGTR1 mRNA. In summary, contrary to previous studies and the observed effects of LPS, we could not demonstrate direct vascular pro-inflammatory effects of Ang II ex vivo or in vitro. As indicated by our results, down-regulation or desensitization of AT R during culture may explain our findings.

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Section: Discussionsupporting

confidence: 90%

Lipopolysaccharides, but not Angiotensin ll, lnduces Direct Pro‐lnflammatory Effects in Cultured Mouse Arteries and Human Endothelial and Vascular Smooth Muscle Cells

Outzen

Zaki

Mehryar

et al. 2017

Basic Clin Pharma Tox

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“…Insepticshock,lipopolysaccharide (LPS)d erived from Gram-negativebacteriac ausesfatalh ypotension and multiple organinjuries [1].LPS hasbeen reported toinduceani nducible nitricoxide synthase( iNOS),which leadst oo verproduction of nitricoxide (NO),a nd producesproinflammatory cytokiness uchast umornecrosisfactor (TNF ) [2,3].Overproduced NO causesvascularhyporeactivity tocontracting stimuli,resulting in hypotension. Onthe otherhand,thereh avebeen many reports on LPS-induced impairmentof endothelium-dependentv asorelaxation (EDR)i nvarious arteries.Inanesthetized rats,L PS caused hypotension and reduced the in situ vasodilatorr esponsetoacetylcholine in the mesentericvascularbed [4,5].In exv ivo experiments, injection of LPS caused hypotension in rats and impaired receptor-dependentand -independentEDR but notNaNO 2 -induced endothelium-independentr elaxation (EIR)i ni solated mesenterica rteries [6].Directv asculareffects of LPS havebeen investigated in in vitro experiments:exposuretoLPS impaired bothreceptordependentand -independentEDR mediated byNO in isolated renal,c oronary and pulmonary arteries [7][8][9], and attenuated the receptor-dependentEDR mediated byendothelium-derived hyperpolarizing factor(EDHF) in mesenterica rteries [10].Inthe presents tudy,we found that in vitro exposuretoLPS inhibited moderately the acetylcholine (ACh)-induced EDR and inhibited markedlys odiumn itroprusside (SNP, NO donor)-in-…”

Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide-induced impairment of nitric oxide-mediated vasorelaxation and protective effects of nitric oxide synthesis inhibitors in isolated rat mesenteric arteries

Miike

Kanda

Kunishiro

et al. 2011

Arzneimittelforschung

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Isolated rat mesenteric arteries were incubated with lipopolysaccharide (LPS) for 6 h and then mounted in an organ bath to investigate their responses to various relaxants. Exposure to LPS moderately reduced acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR), and markedly reduced sodium nitroprusside (SNP)-induced endothelium-independent relaxation (EIR). It did not affect ACh-induced EDR under treatment with a nitric oxide synthase (NOS) inhibitor, which is mediated by an endothelium-derived hyperpolarizing factor (EDHF), and forskolin-induced EIR. N-(3-(Aminomethyl)benzyl)acetamidine (1400 W), an inducible nitric oxide synthase (iNOS) inhibitor, actinomycin D, an RNA polymerase inhibitor, cycloheximide, a protein synthesis inhibitor, and dexamethazone reduced the nitric oxide (NO) production and reversed the reduced ACh-induced EDR and SNP-induced EIR. In LPS-treated mesenteric artery, L-arginine-induced relaxation was not affected by removal of endothelium, indicating muscular inducible nitric oxide synthase (iNOS) induction. Pre-exposure to SNP (NO donor) also moderately reduced ACh-induced EDR and markedly reduced SNP-induced EIR with little effect on ACh-induced EDHF-mediated EDR. In conclusion, in vitro exposure to LPS desensitized vascular smooth muscle cells to endogenous and exogenous NO by overproduction of muscular iNOS-derived NO, and an iNOS inhibitor and iNOS induction inhibitors prevented the LPS-induced desensitization.

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“…e role of bacterial infection has been most studied in studies of the action of bacterial endotoxin causing PAH (see, e.g., [126][127][128][129][130]). Endotoxin exposure is known to produce major increases in NF-B, in�ammatory cytokines, iNOS induction leading to increased NO, ONOO − , and oxidative stress, and not surprisingly, these are all found in studies of endotoxin-induced lung injury including PAH [126][127][128][129][130].…”

Section: Principlementioning

confidence: 99%

“…Endotoxin exposure is known to produce major increases in NF-B, in�ammatory cytokines, iNOS induction leading to increased NO, ONOO − , and oxidative stress, and not surprisingly, these are all found in studies of endotoxin-induced lung injury including PAH [126][127][128][129][130]. Oxidative stress is speci�cally implicated in having a substantial causal role in initiation of PAH [128].…”

Section: Principlementioning

confidence: 99%

Pulmonary Hypertension Is a Probable NO/ONOO⁻Cycle Disease: A Review

Pall

2013

ISRN Hypertension

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e NO/ONOO − cycle is a primarily local biochemical/physiological vicious cycle that appears to cause a series of chronic in�ammatory diseases. is paper focuses on whether the cycle causes pulmonary arterial hypertension (PAH) when located in the pulmonary arteries. e cycle involves 12 elements, including superoxide, peroxynitrite (ONOO − ), nitric oxide (NO), oxidative stress, NF-B, in�ammatory cytokines, iNOS, mitochondrial dysfunction, intracellular calcium, tetrahydrobiopterin depletion, NMDA activity, and TRP receptor activity. 10 of the 12 are elevated in PAH (NMDA?, NO?) and 11 have documented causal roles in PAH. Each stressor that initiates cases of PAH acts to raise cycle elements, and may, therefore, initiate the cycle in this way. PAH involves a primarily local mechanism as required by the cycle and the symptoms and signs of PAH are generated by elements of the cycle. Endothelin-1, which acts as a causal factor in PAH, acts as part of the cycle; its synthesis is stimulated by cycle elements, and it, in turn, increases each element of the cycle. is extraordinary �t to the principles of the NO/ONOO − cycle allows one to conclude that PAH is a NO/ONOO − cycle disease, and this �t supports the cycle as a ma�or paradigm of chronic in�ammatory disease.

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Induced Nitric Oxide Impairs Relaxation but Not Contraction in Endotoxin-Exposed Rat Pulmonary Arteries

Cited by 10 publications

References 30 publications

Lipopolysaccharides, but not Angiotensin ll, lnduces Direct Pro‐lnflammatory Effects in Cultured Mouse Arteries and Human Endothelial and Vascular Smooth Muscle Cells

Lipopolysaccharides, but not Angiotensin ll, lnduces Direct Pro‐lnflammatory Effects in Cultured Mouse Arteries and Human Endothelial and Vascular Smooth Muscle Cells

Lipopolysaccharide-induced impairment of nitric oxide-mediated vasorelaxation and protective effects of nitric oxide synthesis inhibitors in isolated rat mesenteric arteries

Pulmonary Hypertension Is a Probable NO/ONOO⁻Cycle Disease: A Review

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Induced Nitric Oxide Impairs Relaxation but Not Contraction in Endotoxin-Exposed Rat Pulmonary Arteries

Cited by 10 publications

References 30 publications

Lipopolysaccharides, but not Angiotensin ll, lnduces Direct Pro‐lnflammatory Effects in Cultured Mouse Arteries and Human Endothelial and Vascular Smooth Muscle Cells

Lipopolysaccharides, but not Angiotensin ll, lnduces Direct Pro‐lnflammatory Effects in Cultured Mouse Arteries and Human Endothelial and Vascular Smooth Muscle Cells

Lipopolysaccharide-induced impairment of nitric oxide-mediated vasorelaxation and protective effects of nitric oxide synthesis inhibitors in isolated rat mesenteric arteries

Pulmonary Hypertension Is a Probable NO/ONOO−Cycle Disease: A Review

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Pulmonary Hypertension Is a Probable NO/ONOO⁻Cycle Disease: A Review