Nitric Oxide Modulation of Pulmonary Vascular Resistance Is Red Blood Cell Dependent in Isolated Rat Lungs

Uncles, D. R.; Daugherty, Mark O.; Frank, Deborah U.; Roos, C. M.; Rich, George F.

doi:10.1213/00000539-199612000-00014

Cited by 16 publications

(8 citation statements)

References 14 publications

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“…It was reported previously that erythrocytes from either rabbits (31), rats (36,38), or healthy humans (26) are required for the demonstration of flow-induced NO synthesis in isolated perfused lungs. These observations, coupled with the findings that physiological stimuli, such as mechanical deformation (18,26,27,29), stimulate ATP release from erythrocytes and that ATP is a stimulus for endogenous NO synthesis in the isolated Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, when lungs of these species were perfused with either blood (36) or PSS containing washed erythrocytes (30,38), inhibition of endogenous NO synthesis produced a shift in the slope of the pressure-flow relationship consistent with a decrease in vascular caliber, i.e., NO was a determinant of vascular resistance. The ability of the erythrocyte to stimulate NO synthesis in the pulmonary circulation of the rabbit and rat was reported to be independent of effects on viscosity or pressure (31,36). The property of the erythrocyte that was associated with the stimulation of endogenous NO synthesis was shown to be the release of ATP (26,28,30).…”

mentioning

confidence: 93%

“…Physiologically, an alteration in shear applied to the endothelium of blood vessels has been suggested to be a major stimulus for NO release (3,22). However, in the pulmonary circulation, a reappraisal of this viewpoint was required when it was reported that, in isolated rabbit (31) and rat (36,38) lungs perfused with a physiological salt solution (PSS), alterations in shear stress alone did not evoke release of NO. In contrast, when lungs of these species were perfused with either blood (36) or PSS containing washed erythrocytes (30,38), inhibition of endogenous NO synthesis produced a shift in the slope of the pressure-flow relationship consistent with a decrease in vascular caliber, i.e., NO was a determinant of vascular resistance.…”

mentioning

confidence: 99%

“…However, in the pulmonary circulation, a reappraisal of this viewpoint was required when it was reported that, in isolated rabbit (31) and rat (36,38) lungs perfused with a physiological salt solution (PSS), alterations in shear stress alone did not evoke release of NO. In contrast, when lungs of these species were perfused with either blood (36) or PSS containing washed erythrocytes (30,38), inhibition of endogenous NO synthesis produced a shift in the slope of the pressure-flow relationship consistent with a decrease in vascular caliber, i.e., NO was a determinant of vascular resistance. The ability of the erythrocyte to stimulate NO synthesis in the pulmonary circulation of the rabbit and rat was reported to be independent of effects on viscosity or pressure (31,36).…”

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confidence: 99%

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Erythrocytes of humans with cystic fibrosis fail to stimulate nitric oxide synthesis in isolated rabbit lungs

Liang¹,

Stephenson²,

Lonigro³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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Erythrocytes (red blood cells) of either rabbits or healthy humans are required to demonstrate the participation of nitric oxide (NO) in the regulation of pulmonary vascular resistance in the isolated rabbit lung. The property of the erythrocyte that is responsible for the stimulation of NO synthesis was reported to be the ability to release ATP in response to physiological stimuli, including deformation. Moreover, a signal transduction pathway that relates mechanical deformation of erythrocytes to ATP release has been described, and the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is a component, i.e., erythrocytes of individuals with CF do not release ATP in response to deformation. Here, we investigated the hypothesis that, in contrast to those of healthy humans, erythrocytes of humans with CF fail to stimulate endogenous NO synthesis in the isolated rabbit lung. We report that CFTR is a component of the membranes of both rabbit and human erythrocytes. The addition of the NO synthase inhibitor Nω-nitro-l-arginine methyl ester (l-NAME, 100 μM) produced increases in vascular resistance in isolated rabbit lungs perfused with physiological salt solution (PSS) containing erythrocytes of healthy humans, but l-NAME was without effect when the lungs were perfused with PSS alone or PSS containing erythrocytes of CF patients. These results provide support for the hypothesis that, in CF, a defect in ATP release from erythrocytes could lead to decreased endogenous pulmonary NO synthesis and contribute to pulmonary hypertension.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 93%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Erythrocytes of humans with cystic fibrosis fail to stimulate nitric oxide synthesis in isolated rabbit lungs

Liang¹,

Stephenson²,

Lonigro³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…5, 10, and Figure 3). Physiological trapping of NO by erythrocytes involves capture or inactivation of NO by hemes of Hb and serves as an important contributor to HPV (85)(86)(87)(88). NO trapping during hypoxia may be facilitated by regulation of rbc membrane NO permeability via conformation-dependent binding of Hb to the rbc transmembrane protein AE-1 (54).…”

Section: Figurementioning

confidence: 99%

S-nitrosylation: integrator of cardiovascular performance and oxygen delivery

Haldar

Stamler²

2013

J. Clin. Invest.

108

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Delivery of oxygen to tissues is the primary function of the cardiovascular system. NO, a gasotransmitter that signals predominantly through protein S-nitrosylation to form S-nitrosothiols (SNOs) in target proteins, operates coordinately with oxygen in mammalian cellular systems. From this perspective, SNO-based signaling may have evolved as a major transducer of the cellular oxygen-sensing machinery that underlies global cardiovascular function. Here we review mechanisms that regulate S-nitrosylation in the context of its essential role in "systems-level" control of oxygen sensing, delivery, and utilization in the cardiovascular system, and we highlight examples of aberrant S-nitrosylation that may lead to altered oxygen homeostasis in cardiovascular diseases. Thus, through a bird's-eye view of S-nitrosylation in the cardiovascular system, we provide a conceptual framework that may be broadly applicable to the functioning of other cellular systems and physiological processes and that illuminates new therapeutic promise in cardiovascular medicine.

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Nitric Oxide Transport in Blood: A Third Gas in the Respiratory Cycle

Doctor

Stamler

2011

Comprehensive Physiology

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The trapping, processing, and delivery of nitric oxide (NO) bioactivity by red blood cells (RBCs) have emerged as a conserved mechanism through which regional blood flow is linked to biochemical cues of perfusion sufficiency. We present here an expanded paradigm for the human respiratory cycle based on the coordinated transport of three gases: NO, O₂, and CO₂. By linking O₂ and NO flux, RBCs couple vessel caliber (and thus blood flow) to O₂ availability in the lung and to O₂ need in the periphery. The elements required for regulated O₂-based signal transduction via controlled NO processing within RBCs are presented herein, including S-nitrosothiol (SNO) synthesis by hemoglobin and O₂-regulated delivery of NO bioactivity (capture, activation, and delivery of NO groups at sites remote from NO synthesis by NO synthase). The role of NO transport in the respiratory cycle at molecular, microcirculatory, and system levels is reviewed. We elucidate the mechanism through which regulated NO transport in blood supports O₂ homeostasis, not only through adaptive regulation of regional systemic blood flow but also by optimizing ventilation-perfusion matching in the lung. Furthermore, we discuss the role of NO transport in the central control of breathing and in baroreceptor control of blood pressure, which subserve O₂ supply to tissue. Additionally, malfunctions of this transport and signaling system that are implicated in a wide array of human pathophysiologies are described. Understanding the (dys)function of NO processing in blood is a prerequisite for the development of novel therapies that target the vasoactive capacities of RBCs.

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Nitric Oxide Modulation of Pulmonary Vascular Resistance Is Red Blood Cell Dependent in Isolated Rat Lungs

Cited by 16 publications

References 14 publications

Erythrocytes of humans with cystic fibrosis fail to stimulate nitric oxide synthesis in isolated rabbit lungs

Erythrocytes of humans with cystic fibrosis fail to stimulate nitric oxide synthesis in isolated rabbit lungs

S-nitrosylation: integrator of cardiovascular performance and oxygen delivery

Nitric Oxide Transport in Blood: A Third Gas in the Respiratory Cycle

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