Excess nitric oxide does not cause cellular, vascular, or mucosal dysfunction in the cat small intestine

Kubes, Paul; Reinhardt, Paul H.; Payne, Derrice; Woodman, Richard C.

doi:10.1152/ajpgi.1995.269.1.g34

Cited by 31 publications

(31 citation statements)

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“…The view that a drop in endothelial NO production promotes vascular permeability is further supported by the finding that oedema formation was attenuated if the PAF-induced decrease in endothelial NO levels was prevented by imipramine or dexamethasone. Other studies have reported that NO donors also reverse the PAF-induced protein clearance in the intestine [36].…”

Section: Role Of No In Paf-induced Oedema Formationmentioning

confidence: 88%

“…One possible explanation is that this differential regulation of NO represents another example of the frequently contrarian regulatory mechanisms of the systemic and the pulmonary circulation, for example high versus low arterial blood pressure or hypoxic dilatation versus hypoxic constriction. However, that would not explain why NO donors are protective against PAF-induced oedema in both the lungs [16] and the intestine [36]. Alternatively, these differences might be explained in terms of the bell-shaped dose-response curve of NO where either too little or too much NO increases vascular permeability.…”

Section: Role Of No In Paf-induced Oedema Formationmentioning

confidence: 97%

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Platelet-activating factor reduces endothelial nitric oxide production: role of acid sphingomyelinase

Yang¹,

Yin²,

Baumgärtner³

et al. 2009

European Respiratory Journal

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Platelet-activating factor (PAF) is a mediator of pulmonary oedema in acute lung injury that increases vascular permeability within minutes, partly through activation of acid sphingomyelinase (ASM). Since caveolae are rich in sphingomyelin and caveolin-1, which block endothelial nitric oxide (NO) synthase (eNOS) by direct binding, we examined the relationship between ASM, caveolin-1 and eNOS activity in the regulation of vascular permeability by PAF.In caveolar fractions from pulmonary vascular endothelial cells (isolated from perfused rat lungs) the abundance of caveolin-1 and eNOS increased rapidly after PAF perfusion. PAF treatment decreased endothelial NO (eNO) formation as assessed by in situ fluorescence microscopy. Restoration of eNO levels with PAPA-NONOate ((Z)-1-[N-(3-ammoniopropyl)-N-(npropyl)amino]diazen-1-ium-1,2-diolate) mitigated the PAF-induced oedema.PAF treatment increased the ASM activity in caveolar fractions and perfusion with ASM decreased eNO production. Pharmacological inhibition of the ASM pathway with imipramine, D609 or dexamethasone blocked the PAF-induced increase of caveolin-1 and eNOS in caveolae, and the decrease in eNO production and oedema formation.We conclude that PAF causes ASM-dependent enrichment of caveolin-1 in caveolae of endothelial cells, leading to decreased eNO production which contributes to pulmonary oedema formation. These findings suggest rapid reduction in eNO production as a novel mechanism in the regulation of vascular permeability.

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Section: Role Of No In Paf-induced Oedema Formationmentioning

confidence: 88%

Section: Role Of No In Paf-induced Oedema Formationmentioning

confidence: 97%

Platelet-activating factor reduces endothelial nitric oxide production: role of acid sphingomyelinase

Yang¹,

Yin²,

Baumgärtner³

et al. 2009

European Respiratory Journal

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“…Our data show that inhaled NO had absolutely no effect upon the intact peripheral microvasculature or a microvasculature that had ample NO. On the other hand, in a reperfused tissue wherein endothelial NO can be reduced by as much as 90%, for example in the heart or mesentery (3,10,11), inhaled NO provided at least as much protection after ischemia/reperfusion of a distal vascular bed, as does bolus injection or superfusion of tissues with NO donors, however, without the associated hypotension (33,34). In fact, NO inhalation in a very stable and lasting manner returned blood flow to control levels and prevented all of the leukocyte emigration in the most effective way we have observed to date.…”

Section: Discussionmentioning

confidence: 99%

Inhaled NO as a viable antiadhesive therapy for ischemia/reperfusion injury of distal microvascular beds.

Fox-Robichaud

Payne²,

Hasan³

et al. 1998

J. Clin. Invest.

212

135

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Inhaled nitric oxide (NO) is being used more and more in intensive care units as a modality to improve the outcome of patients with pulmonary complications. Our objective was to demonstrate that inhaled NO could impact upon a distally inflamed microvasculature-improving perfusion, leukocyte adhesive interactions, and endothelial dysfunction. Using intravital microscopy to visualize ischemia/reperfusion of postcapillary venules, we were able to demonstrate that the reduction in perfusion, the dramatic increase in leukocyte rolling, adhesion, and emigration, and the endothelial dysfunction could all be significantly abrogated with 80 ppm, but not 20 ppm inhaled NO. Perfusing whole blood directly over an inert P-selectin and CD18 ligand substratum incorporated in a flow chamber recruited the same number of rolling and adhering leukocytes from NO-ventilated and non-NO-ventilated animals, suggesting that inhaled NO was not directly affecting leukocytes. To demonstrate that inhaled NO was actually reaching the peripheral microvasculature in vivo, we applied a NO synthase inhibitor locally to the feline mesentery and demonstrated that the vasoconstriction, as well as leukocyte recruitment, were essentially abolished by inhaled NO, suggesting that a NOdepleted peripheral microvasculature could be replenished with inhaled NO in vivo. Finally, inhaled NO at the same concentration that was effective in ischemia/reperfusion did not affect vascular alterations, leukocyte recruitment, and endothelial dysfunction associated with endotoxemia in the feline mesentery. In conclusion, our data for the first time demonstrate a role for inhaled NO as a therapeutic delivery system to the peripheral microvasculature, showing tremendous efficacy as an antiadhesive, antivasoconstrictive, and antipermeabilizing molecule in NO-depleted tissues, but not normal microvessels or vessels that have an abundance of NO (LPS-treated). The notion that blood borne molecules have NO carrying capacity is conceptually consistent with our observations. ( J. Clin. Invest. 1998. 101:2497-2505.)

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“…15 Although this has not yet been studied in detail, the gram-positive exotox-vascular and mucosal permeability or impair absorption and secretion in the small bowel. 31 However, whether NO donors ins appear to induce NOS expression with a similar, short-…”

Section: Methodsmentioning

confidence: 99%

Long-lasting NO overproduction in cirrhotic patients with spontaneous bacterial peritonitis

et al. 1997

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when cirrhosis is decompensated. [2][3][4][5][6] In vivo studies using veNitric oxide production was studied in cirrhotic panous occlusion plethysmography have shown an overproductients with spontaneous bacterial peritonitis (SBP) or tion of NO related to the hyporesponsiveness to vasoconstricwith other infections. We followed up on the time course tors in cirrhotic patients. 7 However, which specific isoform of of serum nitrate levels in 51 hospitalized patients aged NOS accounts for this increment has not been clearly deterbetween 34 and 81 years. Four groups were defined: pamined. To explain vasodilation in cirrhotic patients, Vallance tients with SBP (group 1, n Å 14), patients with bacterand Moncada have hypothesized that endotoxemia might inemia (group 2, n Å 11), patients with urinary tract infecduce the synthesis and release of NO by iNOS, either directly tion (group 3, n Å 11) and patients in a stable clinical or indirectly via cytokines, and this might therefore account condition (group 4, n Å 20). The four groups did not differ for the hyperdynamic circulatory syndrome associated with in terms of Pugh score (11 { 1, 10 { 1, 11 { 1, and 10 { cirrhosis. 8 This is supported by the findings of Guarner et al. 1, respectively). Serum nitrate levels averaged 31 { 2 that serum levels of nitrate correlated with those found in mmol/L in group 4 (84 samples). On the day results of endotoxemia. 4 On the other hand, endothelial constitutive cytobacteriological examination were positive, mean se-NOS was reported to be up-regulated in rats with CCl 4 -inrum nitrate levels were 75 { 17, 63 { 9, and 36 { 9 mmol/ duced cirrhosis, which suggests a major role of this isoform L, respectively, in groups 1 (17 cases), 2 (11 cases), and in the increased production of NO in cirrhotic rats. 9 The last 3 (11 cases) (P õ .001). The maximum nitrate values repossibility is that both isoforms are involved: a mechanical corded during follow-up were higher in groups 1 (149 { stimulation of endothelial constitutive NOS might be second-15 mmol/L) and 2 (112 { 11 mmol/L) than in group 3 (66 ary to increased cardiac output and shear stress, whereas { 7 mmol/L; P õ .001 and õ.01, respectively). These maxianother source of NO might be from iNOS stimulated biomum values were recorded in all groups approximately chemically through cytokines or endotoxins. weeks after the infection was diagnosed. The meanIn a previous study, we found that 1) patients with ascites duration of NO overproduction, as defined by nitrate had higher nitrate levels than those without ascites and 2) level 3 90 mmol/L, was 15 { 3 days in group 1 and 5 { 1 nitrate levels correlated with orosomucoid, a protein of the day in group 2. When the nitrate concentration was studacute-phase response, which suggests that increased nitrate ied in serum and ascitic fluid sampled on the same day, levels were related to activation of iNOS. 6 The high prevait was found to be higher in ascitic fluid than in serum lence of infectious complications in cirrhotic patients with in eight ca...

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Excess nitric oxide does not cause cellular, vascular, or mucosal dysfunction in the cat small intestine

Cited by 31 publications

References 0 publications

Platelet-activating factor reduces endothelial nitric oxide production: role of acid sphingomyelinase

Platelet-activating factor reduces endothelial nitric oxide production: role of acid sphingomyelinase

Inhaled NO as a viable antiadhesive therapy for ischemia/reperfusion injury of distal microvascular beds.

Long-lasting NO overproduction in cirrhotic patients with spontaneous bacterial peritonitis

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