Nitric oxide as a regulator of tissue oxygen consumption

Wolin, Michael S.; Xie, Yi-Wu; Hintze, Thomas H.

doi:10.1097/00041552-199901000-00015

Cited by 29 publications

(12 citation statements)

References 32 publications

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“…Importantly, there is also evidence that there is an obverse relationship between NO and O 2 in tissue, namely, that NO also acts to decrease tissue O 2 consumption. Specifically, numerous studies have shown that NO is a potent competitive inhibitor of mitochondrial O 2 consumption (17), and, perhaps more importantly, tissue NO production decreases respiration in tissue and also whole animals (40). The possible physiological role of this inhibition has not been uncovered but we suggest one possibility based on our experimental results and computer simulations.…”

Section: Discussionmentioning

confidence: 67%

The biological lifetime of nitric oxide: Implications for the perivascular dynamics of NO and O ₂

Thomas

Kantrow

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

584

180

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Endothelial nitric oxide (nitrogen monoxide) is synthesized at the intravascular͞extravascular interface. We previously have reported the intravascular half-life of NO, as a result of consumption by erythrocytes, as approximately 2 ms. We report here studies designed to estimate the lifetime of NO in the parenchymal (extravascular) tissue and describe the implications of these results for the distribution of NO and oxygen concentration gradients away from the blood vessel. The rate of consumption of NO by parenchymal cells (hepatocytes) linearly depends on both NO and O2 concentration. We estimate that the extravascular half-life of NO will range from 0.09 to > 2 s, depending on O2 concentration and thus distance from the vessel. Computer modeling reveals that this phenomenon, coupled with reversible NO inhibition of cellular mitochondrial oxygen consumption, substantially extends the zone of adequate tissue cellular oxygenation away from the blood vessel, with an especially dramatic effect during conditions of increased tissue work (oxygen consumption). This represents a second action of NO, in addition to vasodilation, in enhancing tissue cellular respiration and provides a possible physiological function for the known reversible inhibition of mitochondrial respiration by low concentrations of NO. Q uite possibly, the two most important properties of nitric oxide (nitrogen monoxide) as a messenger and effector molecule in mammals are its ready diffusibility and its relatively short lifetime (1). With regard to the lifetime of NO, initial measurements using cascade perfusion experiments suggested a disappearance of NO with a lifetime on the order of seconds (2); however, measurements with intact tissue (the coronary circulation) yield a much faster rate, on the order of 0.1 s (3). Although reaction of NO with oxygen (4) is commonly cited as the explanation for this disappearance, this is highly unlikely because it will be too slow with physiologically relevant NO concentrations, even considering the 300-fold acceleration of this process in hydrophobic compartments such as the cell membrane (5). The characteristics of the disappearance of NO by parenchymal cells, which will determine its perivascular diffusion, have not been reported. We have previously characterized the consumption of NO by erythrocytes and estimate that the half-life of NO in the vascular lumen is approximately 2 ms (6). Here we characterize NO consumption by parenchymal cells (isolated rat hepatocytes) and present the implications of these results in terms of the concentration gradients of NO and of O 2 away from a blood vessel. Materials and MethodsChemicals. Chemicals and supplies were from standard sources and were of the highest purity available.Hepatocyte Isolation. Rat hepatocytes were isolated as described (7). Cells were finally resuspended in 10 mM phosphate buffer ϩ 20 mM dextrose, pH 7.4 and kept on ice until use. Viability was Ͼ90% for all experiments, and exposure to NO did not result in appreciable decreases in this number.Measu...

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Section: Discussionmentioning

confidence: 67%

The biological lifetime of nitric oxide: Implications for the perivascular dynamics of NO and O ₂

Thomas

Kantrow

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

584

180

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“…NO produced by Ca 2+ -dependent NOS in endothelium, in cardiomyocytes and in cardiac nerves serves a number of important roles in the regulation of cardiac function including coronary vasodilation, inhibiting platelet and neutrophil actions, antioxidant effects, modulation of cardiac contractile function, and inhibiting cardiac oxygen consumption [ 3,7,[50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67]. In excess concentrations, NO could be potentially toxic.…”

Section: Evidence For Increased Nitrosative Stress In Heart Failurementioning

confidence: 99%

Role of Oxidative-Nitrosative Stress and Downstream Pathways in Various Forms of Cardiomyopathy and Heart Failure

Ungvári¹,

Gupte²,

Recchia³

et al. 2005

CVP

185

125

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Heart failure is the major cause of hospitalization, morbidity and mortality worldwide. Previous experimental and clinical studies have suggested that there is an increased production of reactive oxygen species (ROS: superoxide, hydrogen peroxide, hydroxyl radical) both in animals and in patients with acute and chronic heart failure. The possible source of increased ROS in the failing myocardium include xanthine and NAD(P)H oxidoreductases, cyclooxygenase, the mitochondrial electron transport chain and activated neutrophils among many others. The excessively produced nitric oxide (NO) derived from NO synthases (NOS) has also been implicated in the pathogenesis of chronic heart failure (CHF). The combination of NO and superoxide yields peroxynitrite, a reactive oxidant, which has been shown to impair cardiac function via multiple mechanisms. Increased oxidative and nitrosative stress also activates the nuclear enzyme poly(ADP-ribose) polymerase (PARP), which importantly contributes to the pathogenesis of cardiac and endothelial dysfunction associated with myocardial infarction, chronic heart failure, diabetes, atherosclerosis, hypertension, aging and various forms of shock. Recent studies have demonstrated that pharmacological inhibition of xanthine oxidase derived superoxide formation, neutralization of peroxynitrite or inhibition of PARP provide significant benefit in various forms of cardiovascular injury. This review discusses the role of oxidative/nitrosative stress and downstream pathways in various forms of cardiomyopathy and heart failure.

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“…Testing the hypothesis requires measuring the concentration-dependent effect of bradykinin on respiration. Indeed, experiments have confirmed a decline in respiration in the presence of bradykinin [6,18,19]. Much of the evidence originates from tissue slice experiments using a pharmacological concentration of bradykinin in the range of 0.1-100 μM.…”

Section: No and Respiratory Regulationmentioning

confidence: 99%

Investigation of bioactive NO-scavenging role of myoglobin in myocardium

Kreutzer

Jue

2006

Pflugers Arch - Eur J Physiol

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Because nitric oxide (NO) can react with myoglobin (Mb) to oxidize the heme Fe(II) to Fe(III), the appearance of metmyoglobin (metMb) during bradykinin stimulation underpins the hypothesis that Mb acts as an NO scavenger in the cell. Although some experiments have detected the reporter metMb signal in the -3.7 ppm spectral region, others have not corroborated the finding. Because metMb also has characteristic hyperfine-shifted signals in the 40-100 ppm spectral region, detection of these signals would confirm the presence of metMb. Perfused rat myocardium study has examined this spectral region in a range of bradykinin infusion protocols. Although bradykinin elicits a set of physiological responses, consistent with the induction of NO, the (1)H nuclear magnetic resonance spectra in all experiments reveal no detectable metMb signals. Moreover, in the perfused myocardium model, the bradykinin-induced decline in myocardial oxygen consumption does not appear to arise only from NO binding to cytochrome oxidase.

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Nitric oxide as a regulator of tissue oxygen consumption

Cited by 29 publications

References 32 publications

The biological lifetime of nitric oxide: Implications for the perivascular dynamics of NO and O ₂

The biological lifetime of nitric oxide: Implications for the perivascular dynamics of NO and O ₂

Role of Oxidative-Nitrosative Stress and Downstream Pathways in Various Forms of Cardiomyopathy and Heart Failure

Investigation of bioactive NO-scavenging role of myoglobin in myocardium

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Nitric oxide as a regulator of tissue oxygen consumption

Cited by 29 publications

References 32 publications

The biological lifetime of nitric oxide: Implications for the perivascular dynamics of NO and O 2

The biological lifetime of nitric oxide: Implications for the perivascular dynamics of NO and O 2

Role of Oxidative-Nitrosative Stress and Downstream Pathways in Various Forms of Cardiomyopathy and Heart Failure

Investigation of bioactive NO-scavenging role of myoglobin in myocardium

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Product

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The biological lifetime of nitric oxide: Implications for the perivascular dynamics of NO and O ₂

The biological lifetime of nitric oxide: Implications for the perivascular dynamics of NO and O ₂