Diesel exhaust exposure enhances venoconstriction via uncoupling of eNOS

Knuckles, Travis L.; Lund, Amie K.; Lucas, Selitá; Campen, Matthew J.

doi:10.1016/j.taap.2008.03.010

Cited by 73 publications

(69 citation statements)

References 28 publications

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“…These apparently contradictory findings can be explained by impaired ET-1-induced NO release and are consistent with preclinical evidence of NO-mediated alterations in vascular reactivity to ET-1. 24 We conclude that diesel exhaust inhalation, at levels commonly encountered in the urban environment, does not affect plasma ET-1 concentrations but alters vascular reactivity to ET-1 probably through effects on NO release and bioavailability.…”

Section: Discussionmentioning

confidence: 68%

Contribution of Endothelin 1 to the Vascular Effects of Diesel Exhaust Inhalation in Humans

et al. 2009

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Abstract-Diesel exhaust inhalation impairs vascular function, and, although the underlying mechanism remains unclear, endothelin (ET) 1 and NO are potential mediators. The aim of this study was to identify whether diesel exhaust inhalation affects the vascular actions of ET-1 in humans. In a randomized, double-blind crossover study, 13 healthy male volunteers were exposed to either filtered air or dilute diesel exhaust (331Ϯ13 g/m 3 ). Plasma concentrations of ET-1 and big-ET-1 were determined at baseline and throughout the 24-hour study period. Bilateral forearm blood flow was measured 2 hours after the exposure during infusion of either ET-1 (5 pmol/min) or the ET A receptor antagonist, BQ-123 (10 nmol/min) alone and in combination with the ET B receptor antagonist, BQ-788 (1 nmol/min). Diesel exhaust exposure had no effect on plasma ET-1 and big-ET-1 concentrations (PϾ0.05 for both) or 24-hour mean blood pressure or heart rate (PϾ0.05 for all). ET-1 infusion increased plasma ET-1 concentrations by 58% (PϽ0.01) but caused vasoconstriction only after diesel exhaust exposure (Ϫ17% versus 2% after air; PϽ0.001). In contrast, diesel exhaust exposure reduced vasodilatation to isolated BQ-123 infusion (20% versus 59% after air; PϽ0.001) but had no effect on vasodilatation to combined BQ-123 and BQ-788 administration (PϾ0.05). Diesel exhaust inhalation increases vascular sensitivity to ET-1 and reduces vasodilatation to ET A receptor antagonism despite unchanged plasma ET-1 concentrations. Given the tonic interaction between the ET and NO systems, we conclude that diesel exhaust inhalation alters vascular reactivity to ET-1 probably through its effects on NO bioavailability.

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Section: Discussionmentioning

confidence: 68%

Contribution of Endothelin 1 to the Vascular Effects of Diesel Exhaust Inhalation in Humans

et al. 2009

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“…30 Two animal studies have shown that acute PM exposure reduces NO bioavailability through direct scavenging of NO by ROS and an uncoupling of endothelial NO synthase. 33,34 In vivo evaluation of the NO pathway remains a challenge in vascular research. The laser Doppler imager technique allows different hyperemic tests, such as acetylcholine iontophoresis and heating of the skin, to be evaluated simultaneously.…”

Section: No Bioavailability: Primum Movens Of Diesel Exhaust-mediatedmentioning

confidence: 99%

Acute Exposure to Diesel Exhaust Impairs Nitric Oxide–Mediated Endothelial Vasomotor Function by Increasing Endothelial Oxidative Stress

et al. 2013

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Abstract-Exposure to diesel exhaust was recently identified as an important cardiovascular risk factor, but whether it impairs nitric oxide (NO)-mediated endothelial function and increases production of reactive oxygen species (ROS) in endothelial cells is not known. We tested these hypotheses in a randomized, controlled, crossover study in healthy male volunteers exposed to ambient and polluted air (n=12). The effects of skin microvascular hyperemic provocative tests, including local heating and iontophoresis of acetylcholine and sodium nitroprusside, were assessed using a laser Doppler imager. Before local heating, skin was pretreated by iontophoresis of either a specific NO-synthase inhibitor (L-N-arginine-methyl-ester) or a saline solution (Control). ROS production was measured by chemiluminescence using the lucigenin technique in human umbilical vein endothelial cells preincubated with serum from 5 of the subjects. Exposure to diesel exhaust reduced acetylcholine-induced vasodilation (P<0.01) but did not affect vasodilation with sodium nitroprusside. Moreover, the acetylcholine/sodium nitroprusside vasodilation ratio decreased from 1.51±0.1 to 1.06±0.07 (P<0.01) and was correlated to inhaled particulate matter 2.5 (r=−0.55; P<0.01). NO-mediated skin thermal vasodilatation decreased from 466±264% to 29±123% (P<0.05). ROS production was increased after polluted air exposure (P<0.01) and was correlated with the total amount of inhaled particulate matter <2.5 μm (PM2.5). In healthy subjects, acute experimental exposure to diesel exhaust impaired NO-mediated endothelial vasomotor function and promoted ROS generation in endothelial cells. Increased PM2.5 inhalation enhances microvascular dysfunction and ROS production.

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“…Recent studies have demonstrated a role for dysfunction in vascular endothelial nitric oxide synthase (eNOS) signaling in mediating increased susceptibility to cardiovascular disease in response to environmental exposure to inhaled species that can promote oxidative tissue injury (e.g., cigarette smoke, diesel, or ozone) (18)(19)(20)(21). Nitric oxide produced from eNOS plays a central role in vascular homeostasis mechanisms, including regulating vessel tone and cellular respiration, inhibiting smooth muscle proliferation, and maintaining an antithrombotic and antiinflammatory luminal surface (22,23).…”

mentioning

confidence: 99%

Chlorine Gas Exposure Causes Systemic Endothelial Dysfunction by Inhibiting Endothelial Nitric Oxide Synthase–Dependent Signaling

Honavar

Samal

Bradley

et al. 2011

Am J Respir Cell Mol Biol

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Chlorine gas (Cl 2 ) exposure during accidents or in the military setting results primarily in injury to the lungs. However, the potential for Cl 2 exposure to promote injury to the systemic vasculature leading to compromised vascular function has not been studied. We hypothesized that Cl 2 promotes extrapulmonary endothelial dysfunction characterized by a loss of endothelial nitric oxide synthase (eNOS)-derived signaling. Male Sprague Dawley rats were exposed to Cl 2 for 30 minutes, and eNOS-dependent vasodilation of aorta as a function of Cl 2 dose (0-400 ppm) and time after exposure (0-48 h) were determined. Exposure to Cl 2 (250-400 ppm) significantly inhibited eNOS-dependent vasodilation (stimulated by acetycholine) at 24 to 48 hours after exposure without affecting constriction responses to phenylephrine or vasodilation responses to an NO donor, suggesting decreased NO formation. Consistent with this hypothesis, eNOS protein expression was significantly decreased (z 60%) in aorta isolated from Cl 2 -exposed versus airexposed rats. Moreover, inducible nitric oxide synthase (iNOS) mRNA was up-regulated in circulating leukocytes and aorta isolated 24 hours after Cl 2 exposure, suggesting stimulation of inflammation in the systemic vasculature. Despite decreased eNOS expression and activity, no changes in mean arterial blood pressure were observed. However, injection of 1400W, a selective inhibitor of iNOS, increased mean arterial blood pressure only in Cl 2 -exposed animals, suggesting that iNOS-derived NO compensates for decreased eNOS-derived NO. These results highlight the potential for Cl 2 exposure to promote postexposure systemic endothelial dysfunction via disruption of vascular NO homeostasis mechanisms.

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Diesel exhaust exposure enhances venoconstriction via uncoupling of eNOS

Cited by 73 publications

References 28 publications

Contribution of Endothelin 1 to the Vascular Effects of Diesel Exhaust Inhalation in Humans

Contribution of Endothelin 1 to the Vascular Effects of Diesel Exhaust Inhalation in Humans

Acute Exposure to Diesel Exhaust Impairs Nitric Oxide–Mediated Endothelial Vasomotor Function by Increasing Endothelial Oxidative Stress

Chlorine Gas Exposure Causes Systemic Endothelial Dysfunction by Inhibiting Endothelial Nitric Oxide Synthase–Dependent Signaling

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