Exhaled nitric oxide as a marker for organic nitrate tolerance.

Husain, M.; Adrie, Christophe; Ichinose, Fumito; Kavosi, Melahat; Zapol, Warren M.

doi:10.1161/01.cir.89.6.2498

Cited by 49 publications

(27 citation statements)

References 12 publications

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“…43,44 Our study has extended these observations and suggests that monitoring GTN-induced exhaled NO could be used to assess primary and secondary nitrate tolerance in the clinical setting. 37 Although these observations clearly demonstrate pulmonary microvascular injury during lung transplantation, the exact molecular mechanisms, the implications to microvascular reactivity and endothelial permeability, and overall clinical relevance remain to be uncovered. Our working hypothesis is that increased oxidative stress is responsible for NO attenuation and the activity of NO pathways could be restored by appropriate anti-oxidant therapy.…”

Section: Discussionmentioning

confidence: 99%

“…24,26 To further investigate the fate of NO pathways in the microvascular lung compartment, one can deliver exogenous NO to the pulmonary circulation and monitor evolution of this NO in exhaled breath. 18,23,[35][36][37] We have suggested that GTN-induced exhaled NO might be a useful tool to monitor metabolic function of the pulmonary microvasculature. This proposed test has numerous clinical, diagnostic and mechanistic advantages and could compliment the current clinical diagnostic efforts.…”

Section: Discussionmentioning

confidence: 99%

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Dynamics of Nitroglycerin-induced Exhaled Nitric Oxide After Lung Transplantation: Evidence of Pulmonary Microvascular Injury?

Gál

Kovesi

Royston

et al. 2007

The Journal of Heart and Lung Transplantation

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Background:In search of real-time molecular correlates to ischemia-reperfusion-induced lung injury, we explored the hypothesis that liberation of nitric oxide (NO) into exhaled breath after pulmonary microvascular bioconversion of nitroglycerin (GTN) is attenuated in clinical lung transplantation. Methods:Exhaled NO was measured under basal conditions and after intravenous administration of GTN in patients undergoing lung transplantation. Patients undergoing routine cardiac surgery served as controls. Basal and GTN-induced exhaled NO was also measured in donors before retrieval and after implantation in recipients. Results:The characteristic GTN-induced exhaled NO response observed in cardiac surgical patients before cardiopulmonary bypass and in lung transplant and multiple-organ donors was nearly totally abolished in lung transplant recipients. This response was also attenuated to a lesser degree in the routine cardiac surgery patients after cardiopulmonary bypass. Conclusions: These results suggest a graded influence of time-factored complete and partial ischemia on GTN-induced evolution of NO into exhaled breath, providing biochemical evidence for a degree of microvascular injury, which can be monitored non-invasively at the bedside.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dynamics of Nitroglycerin-induced Exhaled Nitric Oxide After Lung Transplantation: Evidence of Pulmonary Microvascular Injury?

Gál

Kovesi

Royston

et al. 2007

The Journal of Heart and Lung Transplantation

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“…[11][12][13][14][15][16] and suggested that exhaled NO during exercise can be a marker of spilled NO from the pulmonary vasculature. Another study demonstrated that the decrease in exhaled NO was associated with diminished vasodilation in a nitroglycerin tolerance test, 23 which supported a linkage of endothelium function with exhaled NO. Based on these observations, the present study hypothesized that exhaled NO output may be linked to impaired oxygen kinetics at the onset of exercise, caused by an insufficient increase in cardiac output in patients with CHF.…”

Section: Background and Hypothesismentioning

confidence: 91%

Increased Exhaled Nitric Oxide and Impaired Oxygen Uptake (VO<sub>2</sub>) Kinetics During Exercise in Patients With Chronic Heart Failure

1999

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itric oxide (NO) is an important modulator of biological function in physiologic and pathologic states. It exerts blood flow regulation, blood pressure control, platelet aggregation and vascular remodeling. 1-3 Congestive heart failure (CHF) is characterized by peripheral circulatory failure caused by cardiac pump dysfunction and/or excessive vasoconstrictive stimuli despite augmented vasodilating factors. 4 It is well known that the vasodilation to endothelium-dependent vasodilating stimuli is blunted in CHF. Insufficient endotheliumderived vasodilating reserve, however, can be caused by diminished NO release or increased basal NO production, which is an issue in CHF. [5][6][7][8][9] A recent study demonstrated that endogenous NO is detectable in the range of parts per billion (ppb) in the exhaled air of animals and humans. 10 Exercise enhances exhaled NO output in healthy subjects [11][12][13][14][15][16] and it is suspected that this exercise-induced elevation in exhaled NO is linked to cardiovascular activation during exercise. Oxygen kinetics determined at the onset of exercise (ie, oxygen deficit and time constant for oxygen uptake (V • O2) increment) are a marker of cardiac output response 17 and are characteristically impaired in patients with CHF. [17][18][19][20] One can hypothesize that abnormal endothelial function may be linked to abnormal blood flow response and abnor-

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“…13 Exhaled NO levels have also been found to increase with exercise 14 and in response to orally administered L-arginine 15 and intravenously infused nitroglycerin. 16 Conversely, the exhaled NO level is decreased in patients with heart failure, 17 hypertension, 18 and acute respiratory distress syndrome. 19 The exhaled NO level is also reduced by smoking.…”

Section: Sumino Et Al Enalapril Increases Exhaled Nitric Oxidementioning

confidence: 99%

Effect of Enalapril on Exhaled Nitric Oxide in Normotensive and Hypertensive Subjects

Sumino

Nakamura²,

Kanda³

et al. 2000

Hypertension

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Abstract-We investigated whether an angiotensin-converting enzyme (ACE) inhibitor increases the production of nitric oxide (NO) in exhaled air in normotensive and hypertensive subjects. In study 1, 8 normotensive male subjects received a single oral dose of enalapril (5 mg) or nitrendipine (10 mg) in a crossover manner. Exhaled air was collected at baseline, and at 2, 4, and 8 hours after administration of the drug. In study 2, 10 normotensive subjects (6 men and 4 women) and 10 hypertensive subjects (6 men and 4 women) received a single oral dose of enalapril (5 mg). Exhaled air was collected at baseline and at 2 and 4 hours after administration of the drug. In study 1, enalapril significantly increased the NO release rate from the lung in normotensive subjects (36.9Ϯ5.1 pmol/s at baseline versus 58.3Ϯ7.3 pmol/s at 4 hours, PϽ0.01). Nitrendipine did not change the NO release rate. In study 2, enalapril significantly increased the release of NO from the lung in normotensive subjects (40.4Ϯ6.0 pmol/s at baseline versus 70.3Ϯ11.4 pmol/s at 4 hours, PϽ0.01) but not in hypertensive subjects. ACE inhibition increased NO production from the lung in normotensive subjects but not in hypertensive patients. The reduction of angiotensin II production and/or the accumulation of bradykinin in the pulmonary tissue may be responsible for increased NO production in components of the lung, such as the pulmonary vascular endothelium, bronchial epithelial cells, macrophages, nasopharyngeal cells, and neurons. However, the effects of ACE inhibition on NO production from the lung differ between hypertensive subjects and normotensive subjects. Key Words: angiotensin Ⅲ bradykinin Ⅲ hypertension, essential Ⅲ nitric oxide E ndothelium-derived relaxing factor (EDRF) has been identified as nitric oxide (NO), a potent vasodilator. 1 The attenuated endothelium-dependent vasodilation in patients with essential hypertension 2 may be largely mediated by a decrease in the release or activity of NO. Decreased endothelial NO is considered to be either a cause or a consequence of hypertension.NO is a highly unstable substance with a plasma half-life of only a few seconds 3 ; therefore, its direct measurement is difficult, particularly in vivo. Endogenously produced NO is assessed by measuring the serum levels of NOx, the products of NO metabolism, or by measuring endogenous NO present in expired air. The presence of endogenous NO in exhaled air has been demonstrated in humans. 4 The cellular source of exhaled NO is not known, but it has been proposed that all NO synthase isoforms in the respiratory system contribute to NO release. 5 Therefore, the amount of NO in expired air is an appropriate indicator of endogenously produced NO in the lung. We recently developed a method for measuring NO in exhaled air. 6 Angiotensin-converting enzyme (ACE) inhibitors improve impaired endothelium-dependent vascular relaxation in rats, 7 but this effect of ACE inhibitors is not always demonstrated in humans. 8,9 However, it has not yet been established whether or...

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Exhaled nitric oxide as a marker for organic nitrate tolerance.

Cited by 49 publications

References 12 publications

Dynamics of Nitroglycerin-induced Exhaled Nitric Oxide After Lung Transplantation: Evidence of Pulmonary Microvascular Injury?

Dynamics of Nitroglycerin-induced Exhaled Nitric Oxide After Lung Transplantation: Evidence of Pulmonary Microvascular Injury?

Increased Exhaled Nitric Oxide and Impaired Oxygen Uptake (VO<sub>2</sub>) Kinetics During Exercise in Patients With Chronic Heart Failure

Effect of Enalapril on Exhaled Nitric Oxide in Normotensive and Hypertensive Subjects

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