ATP: the red blood cell link to NO and local control of the pulmonary circulation

1996 ◽  
Vol 271 (6) ◽  
pp. H2717-H2722 ◽  
Author(s):  
R. S. Sprague ◽  
M. L. Ellsworth ◽  
A. H. Stephenson ◽  
A. J. Lonigro
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Blood Cell ◽  
Local Control ◽  
Blood Cells ◽  
Mechanical Deformation ◽  
Pressure Flow ◽  
Human Rbcs ◽  
Unique Mechanism ◽  
Stimulation Of

Recently, we reported that rabbit red blood cells (RBCs) were required for the expression of nitric oxide (NO) activity on pulmonary vascular resistance (PVR) in rabbit lungs. Here, we investigate the hypothesis that RBCs participate in the regulation of PVR via release of ATP in response to mechanical deformation that, in turn, evokes vascular NO synthesis. We found that rabbit and human RBCs, but not dog RBCs, release ATP in response to mechanical deformation. To determine the contribution of this ATP to NO synthesis and PVR, we compared the effects of human and dog RBCs on pressure-flow relationships in isolated rabbit lungs. In the presence of human RBCs, NG-nitro-L-arginine methyl ester (100 microM) produced a shift in the pressure-flow relationship consistent with a reduction in vascular caliber. NG-nitro-L-arginine methyl ester had no effect in lungs perfused with dog RBCs. These results suggest a unique mechanism for the control of PVR in rabbits and humans whereby release of ATP by RBCs in response to mechanical deformation leads to stimulation of NO synthesis that, in turn, modulates the PVR.

scholarly journals Concanavalin A-mediated binding and sphering of human red blood cells by homologous monocytes.

1976 ◽  
Vol 144 (6) ◽  
pp. 1695-1700 ◽  
Author(s):  
D Guerry ◽  
M A Kenna ◽  
A D Schrieber ◽  
R A Cooper
Keyword(s):  
Blood Cell ◽  
Red Blood Cells ◽  
Concanavalin A ◽  
Blood Cells ◽  
Human Monocytes ◽  
Blood Monocytes ◽  
Con A ◽  
Peripheral Blood Monocytes ◽  
Human Red Blood Cells ◽  
Human Rbcs

Human red blood cells sensitized with concanavalin A became bound to homologous peripheral blood monocytes. Binding occured at a concentration of 10(5) molecules of tetrameric Con A per red blood cell (RBC) and increased with additional Con A. RBC binding began within 5 min and was maximal at 90 min. Phagocytosis of sensitized RBCs was minimal. RBC attachment was prevented by 0.01 M alpha-methyl-D-mannopyranoside, and, once the RBC-monocyte rosette was established, bound RBCs were largely removed with this specific saccharide inhibitor of Con A. RBCs attached to monocytes became spherocytic and osmotically fragile. The recognition of concanavalin A (Con A)-coated RBCs was not mediated through the monocyte IgG-Fc receptor. These studies demonstrate that, like IgG and C3b, Con A is capable of mediating the binding of human RBCs to human monocytes. Red cells so bound are damaged at the monocyte surface.

Deformation-induced ATP release from red blood cells requires CFTR activity

1998 ◽  
Vol 275 (5) ◽  
pp. H1726-H1732 ◽  
Author(s):  
Randy S. Sprague ◽  
Mary L. Ellsworth ◽  
Alan H. Stephenson ◽  
Mary E. Kleinhenz ◽  
Andrew J. Lonigro
Keyword(s):  
Cystic Fibrosis ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Atp Release ◽  
Chronic Obstructive Lung Disease ◽  
Mechanical Deformation ◽  
Chronic Obstructive ◽  
Healthy Humans ◽  
Human Red Blood Cells ◽  
Human Rbcs

Recently, it was reported that rabbit and human red blood cells (RBCs) release ATP in response to mechanical deformation. Here we investigate the hypothesis that the activity of the cystic fibrosis transmembrane conductance regulator (CFTR), a member of the ATP binding cassette, is required for deformation-induced ATP release from RBCs. Incubation of rabbit RBCs with either of two inhibitors of CFTR activity, glibenclamide (10 μM) or niflumic acid (20 μM), resulted in inhibition of deformation-induced ATP release. To demonstrate the contribution of CFTR to deformation-induced ATP release from human RBCs, cells from healthy humans, patients with cystic fibrosis (CF), or patients with chronic obstructive lung disease (COPD) unrelated to CF were studied. RBCs of healthy humans and COPD patients released ATP in response to mechanical deformation. In contrast, deformation of RBCs from patients with CF did not result in ATP release. We conclude that deformation-induced ATP release from rabbit and human RBCs requires CFTR activity, suggesting a previously unrecognized role for CFTR in the regulation of vascular resistance.

scholarly journals Extracellular ATP signaling in the rabbit lung: erythrocytes as determinants of vascular resistance

2003 ◽  
Vol 285 (2) ◽  
pp. H693-H700 ◽  
Author(s):  
Randy S. Sprague ◽  
Jeffrey J. Olearczyk ◽  
Dana M. Spence ◽  
Alan H. Stephenson ◽  
Robert W. Sprung ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Vascular Resistance ◽  
Flow Rate ◽  
Vascular Endothelium ◽  
Pulmonary Circulation ◽  
Blood Cells ◽  
Atp Release ◽  
Rabbit Lung ◽  
Atp Signaling

Previously, it was reported that red blood cells (RBCs) are required to demonstrate participation of nitric oxide (NO) in the regulation of rabbit pulmonary vascular resistance (PVR). RBCs do not synthesize NO; hence, we postulated that ATP, present in millimolar amounts in RBCs, was the mediator, which evoked NO synthesis in the vascular endothelium. First, we found that deformation of RBCs, as occurs on passage across the pulmonary circulation with increasing flow rate, evoked increments in ATP release. Here, ATP (300 nM), administered to isolated, salt solution-perfused (PSS) rabbit lungs, decreased total and upstream (arterial) PVR, a response inhibited by NG-nitro-l-arginine methyl ester (l-NAME, 100 μM). In lungs perfused with PSS containing RBCs, l-NAME increased total and upstream PVR. In lungs perfused with PSS containing glibenclamide-treated RBCs, which inhibits ATP release, l-NAME was without effect. Apyrase grade VII (8 U/ml), which degrades ATP to AMP, was without effect on PVR in PSS-perfused lungs. These results are consistent with the hypothesis that ATP, released from RBCs as they traverse the pulmonary circulation, evokes endogenous NO synthesis.

Blood Cell Versus Vascular Endothelial Cell Contributions to Nitrite Homeostasis and Blood Pressure Regulation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4601-4601
Author(s):  
Katherine C Wood ◽  
Virginia B Liu ◽  
Audrey Noguchi ◽  
Xunde Wang ◽  
Nalini Raghavachari ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Blood Cell ◽  
Whole Blood ◽  
Blood Cells ◽  
Pressure Regulation ◽  
Chimeric Mice ◽  
Blood Pressures ◽  
Plasma Nitrite ◽  
Positive Controls

Abstract Mice genetically deficient in constitutive nitric oxide synthase (eNOS) are hypertensive compared to normal C57Bl6 (wild type) mice, indicating the importance of constitutively produced nitric oxide (NO•) to blood pressure regulation and vascular homeostasis. The objective of this study was to use molecular methodologies to determine the contribution of eNOS in circulating blood cells to the intravascular pool of nitrite, a metabolite and storage form of nitric oxide (NO•) with powerful vasorelaxant activity, and to the regulation of blood pressure under physiological conditions. We used bone marrow transplant to create chimeric mice genetically deficient in eNOS in either circulating blood cells (−/+) or vascular endothelium (+/−), confirmed by flow cytometry, western blot, RT-PCR and immunohistochemistry. Nitrite concentrations in whole blood and plasma of chimeras were quantified using ozone-based reductive chemiluminescence. Mean arterial and diastolic blood pressures of chimeras were assessed in the absence/presence of NOS stimulation with oral L-Arginine or NOS inhibition with oral L-Name. A highly significant inverse correlation between plasma nitrite concentrations and blood pressures was noted across all groups of chimeric mice. Importantly, in agreement with higher blood pressures in −/+ chimeras compared to eNOS positive controls (+/+ chimeras globally competent for eNOS), significantly reduced whole blood and plasma nitrite concentrations were also measured. Blood pressure responses to NOS inhibition or stimulation were intact in all chimera groups except eNOS negative controls (−/− chimeras globally deficient for eNOS) and, importantly, blunted in −/+ chimeras compared to eNOS positive controls. These findings indicate a functional blood cell eNOS that is a major contributor to circulating nitrite concentrations and plays a critical role in vascular homeostasis.

Stimulation of α2Adrenoceptors Dilates the Rat Middle Cerebral Artery

1996 ◽  
Vol 85 (1) ◽  
pp. 82-90 ◽  
Author(s):  
Robert M. Bryan ◽  
M. Y. Eichler ◽  
M. W. G. Swafford ◽  
T. D. Johnson ◽  
M. S. Suresh ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Pertussis Toxin ◽  
Saline Solution ◽  
Cerebral Arteries ◽  
Middle Cerebral Arteries ◽  
Physiologic Saline ◽  
Stimulation Of

Background Because alpha 2 adrenoceptor agonists are used as adjuncts to anesthetics, their effects on the cerebrovascular circulation are of prime importance. We studied changes in the diameter of rat middle cerebral arteries after stimulation of alpha 2 adrenoceptors with UK14,304. Methods Rat middle cerebral arteries were isolated, cannulated at each end with a glass micropipette, and pressurized to 85 mmHg. The middle cerebral arteries were immersed in a bath (37 degrees C) containing physiologic saline solution, and luminally perfused with physiologic saline solution (100 microliters/ min). Changes in vessel diameter were measured after magnification with a microscope. Results Resting diameter of the middle cerebral arteries was 239 +/- 13 microns (n = 8) for the first study. A dose-dependent dilation was produced by addition of UK14,304 to the extraluminal bath; a 10-15% increase in diameter occurred at a concentration of 10(-4)M. The dilations produced by UK14,304 were blocked with selective alpha 2-antagonists, idazoxan and rauwolscine, but not by the selective alpha 1-antagonist, prazosin. The dilations could be blocked by removal of the endothelium, or the nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (10(-5) M). The inhibitory effects of N-nitro-L-arginine methyl ester were reversed with the addition of 10(-3) M L-arginine, but not 10(-3) M D-arginine. Furthermore the dilation produced by UK14,304 was completely abolished with pertussis toxin (100 ng/ml). Conclusions It was concluded that the stimulation of alpha 2 adrenoceptors with UK14,304 produced a dilation in the rat middle cerebral artery that (1) was dependent on intact endothelium, (2) involved nitric oxide, and (3) acted via a pertussis toxin-sensitive G protein.

5-HT-induced colonic contractions: enteric locus of action and receptor subtypes

1997 ◽  
Vol 273 (1) ◽  
pp. G68-G74 ◽  
Author(s):  
S. Graf ◽  
S. K. Sarna
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Contractile Response ◽  
No Synthase ◽  
Enteric Neurons ◽  
Receptor Subtypes ◽  
Arterial Infusion ◽  
Stimulation Of

The role of 5-hydroxytryptamine (5-HT), its enteric locus of action, and the receptor subtypes involved in the stimulation of in vivo phasic contractions in the colon were investigated by close intra-arterial infusions in conscious dogs. The contractile response to 5-HT was blocked completely by prior close intra-arterial infusion of atropine and reduced significantly by prior close intra-arterial infusions of tetrodotoxin and hexamethonium. The contractile response was, however, enhanced by the inhibition of nitric oxide (NO) synthase by a prior close intra-arterial infusion of N omega-nitro-L-arginine methyl ester. Prior close intra-arterial infusions of 5-HT1A/5-HT1B, 5-HT2A, 5-HT2C, and 5-HT4 receptor antagonists had no significant effect on the contractile response to 5-HT. By contrast, 5-HT3 receptor antagonist significantly and dose dependently inhibited the contractile response to 5-HT. We conclude that the in vivo phasic contractile response to 5-HT in the colon is mediated mainly by 5-HT3 receptors located on pre- and postsynaptic cholinergic enteric neurons. 5-HT receptors may also be localized on nonadrenergic, noncholinergic inhibitory motoneurons that use NO as a neurotransmitter.

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