Direct Measurement of Nitric Oxide Production in Platelets: Relationship with Cytosolic Ca2+ Concentration

Lantoine, Frédérique; Brunet, Annie; Bedioui, Féthi; Devynck, Jacques; Devynck, Marie‐Aude

doi:10.1006/bbrc.1995.2540

Cited by 78 publications

(47 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6,15 We also previously showed that the electrode used in this study was sufficiently sensitive to detect the release of NO from aggregated platelets on the basis of the following findings. 5 First, S-nitroso-N-acetyl-dl-penicillamine, a direct NO donor, dose-dependently increased the electrical current.…”

Section: Discussionmentioning

confidence: 52%

Platelet-Derived Nitric Oxide and Coronary Risk Factors

et al. 2000

View full text Add to dashboard Cite

Abstract-Platelet aggregation is inhibited through a negative feedback mechanism by the L-arginine/nitric oxide (NO) pathway found in platelets themselves. We have shown that long-term smoking impairs the bioactivity of platelet-derived NO (PDNO), resulting in an increased platelet aggregability. However, little is known about the relation between other coronary risk factors and PDNO release. Accordingly, this study was undertaken to examine whether other coronary risk factors are related to the impairment of PDNO bioactivity. We measured collagen-induced PDNO release with an NO-selective electrode in 61 subjects (mean age 47 years, range 24 to 74 years) who underwent complete physical and laboratory examinations. There was a significant inverse correlation between PDNO release and the number of coronary risk factors (rϭϪ0. Key Words: platelets Ⅲ nitric oxide Ⅲ risk factors Ⅲ atherothrombosis P latelets possess the functional L-arginine/nitric oxide (NO) pathway via constitutive NO synthase. 1,2 Platelet-derived NO (PDNO) increases the intraplatelet level of cGMP and inhibits platelet aggregation. 1 This modulation of platelet aggregation via the L-arginine/NO pathway is recognized as a negative-feedback mechanism to inhibit aggregation. 3,4 Using an NO-selective electrode, we 5 and others 6 directly measured PDNO release during platelet aggregation, which was potentiated by L-arginine and attenuated by inhibitors of NO synthase, indicating the existence of an L-arginine/NO pathway in human platelets. 1,7 PDNO has been shown to play a functional role in the inhibition of not only platelet activation but also platelet recruitment after aggregation. 8 Recently, we have shown that long-term smoking impairs PDNO release, resulting in an increased platelet aggregability. 5 However, little is known about the relation between other coronary risk factors and PDNO release. Accordingly, the present study was undertaken to investigate the hypothesis that other coronary risk factors impair platelet function and thereby affect PDNO release in subjects with major risk factors. Methods Study SubjectsThe study population consisted of 61 subjects who agreed to participate in the study. The subjects underwent complete routine physical and laboratory examinations, and their complete anamnesis was obtained. Of the 61 subjects, 42 were healthy volunteers, 12 had stable effort angina, and 7 had previous myocardial infarction. Medications, including long-acting nitrates, calcium channel blockers, ␤-blockers, and ACE inhibitors, were withheld for Ն24 hours, and aspirin was withheld for Ն1 week before the study. None of the patients had received cholesterol-lowering agents. Patients with acute coronary syndromes, valvular heart diseases, or heart failure were excluded from the study. The present protocol was approved by our institutional ethic committee, and informed consent for the study was obtained from all patients. Definition of Coronary Risk FactorsCoronary risk factors in this study were determined according to the Sixth Report o...

show abstract

Section: Discussionmentioning

confidence: 52%

Platelet-Derived Nitric Oxide and Coronary Risk Factors

et al. 2000

View full text Add to dashboard Cite

show abstract

“…Thus, studies using Western blots of cytosolic and membrane fractions of human platelets as well as sequential affinity chromatography were able to confirm the presence of a Ca 2+ /CAM dependent isoform similar to the eNOS (Sase, Michel, 1995;Muruganandam, Mutus, 1994). These results are also supported by spectroscopic determination (Radomski et al, 1990b), eletrochemical NO detection (Lantoine et al, 1995) and porphyrinic microsensor assay (Malinski et al, 1993), after platelet stimulation with collagen. In addition, there is evidence for an inducible isoform in human platelet NOS using reverse transcription polymerase chain reaction (Mehta et al, 1995;Berkels et al, 1997).…”

Section: Introductionmentioning

confidence: 57%

Human platelet nitric oxide synthase activity: an optimized method

Kawamato¹,

Glezer²,

Munhoz³

et al. 2002

Rev. Bras. Cienc. Farm.

View full text Add to dashboard Cite

show abstract

“…Platelet activation stimulates endogenous ⅐ NO generation rates of between 0.004 and 1.35 nmol⅐min Ϫ1 10 8 platelets Ϫ1 (43,44,46). Herein, platelet ⅐ NO consumption of 0.1-0.4 nmol⅐min Ϫ1 ⅐10 8 platelets Ϫ1 or 0.8 Ϯ 0.17 M by thrombin-activated PRP indicates that platelet ⅐ NO removal will significantly impair ⅐ NO-dependent signaling during aggregation.…”

Section: Discussionmentioning

confidence: 89%

Catalytic Consumption of Nitric Oxide by Prostaglandin H Synthase-1 Regulates Platelet Function

O'Donnell¹,

Coles²,

Lewis³

et al. 2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

Nitric oxide ( ⅐ NO) plays a central role in vascular homeostasis via regulation of smooth muscle relaxation and platelet aggregation. Although mechanisms for ⅐ NO formation are well known, removal pathways are less well characterized, particularly in cells that respond to ⅐ NO through activation of soluble guanylate cyclase. Herein, we report that ⅐ NO is catalytically consumed by prostaglandin H synthase-1 (PGHS-1) through acting as a reducing peroxidase substrate. With purified ovine PGHS-1, ⅐ NO consumption requires peroxide (LOOH or H 2 O 2 ), with a K m (app) for 15(S)hydroperoxyeicosatetraenoic acid (HPETE) of 3.27 ؎ 0.35 M. During this, 2 mol ⅐ NO are consumed per mol HPETE, and loss of HPETE hydroperoxy group occurs with retention of the conjugated diene spectrum. Hydroperoxide-stimulated ⅐ NO consumption requires heme incorporation, is not inhibited by indomethacin, and is further stimulated by the reducing peroxidase substrate, phenol. PGHS-1-dependent ⅐ NO consumption also occurs during arachidonate, thrombin, or A23187 activation of platelets (1-2 M⅐min ؊1 for typical plasma platelet concentrations) and prevents ⅐ NO stimulation of platelet soluble guanylate cyclase. Platelet sensitivity to ⅐ NO as an inhibitor of aggregation is greater using a platelet-activating stimulus (U46619) that does not cause ⅐ NO consumption, indicating that this mechanism overcomes the anti-aggregatory effects of ⅐ NO. Catalytic consumption of ⅐ NO during eicosanoid synthesis thus represents both a novel proaggregatory function for PGHS-1 and a regulated mechanism for vascular ⅐ NO removal.In the vasculature, strict control of nitric oxide ( ⅐ NO) bioactivity is essential for both maintaining vascular tone and inhibiting platelet aggregation. Reaction with oxyhemoglobin (oxyHb) 1 is generally viewed to be the major fate of ⅐ NO generated in the vasculature. However, recent work has shown that erythrocyte sequestration of hemoglobin, combined with flow, decreases oxyHb reaction with ⅐ NO and thus renders it less effective at antagonizing ⅐ NO bioactivity in the vessel lumen (1, 2). Also, the biological half-life of ⅐ NO, when determined under oxyHb-free conditions (0.1-3 s), is far shorter than expected rates of ⅐ NO autooxidation (3, 4). Both of these observations indicate that cell-dependent catalytic scavenging reactions will play a role in regulating ⅐ NO signaling. Under pathological conditions of vascular dysfunction, accelerated ⅐ NO loss is often observed (5-7). In hypertensive states, a role for superoxide (O 2 . ) reacting with ⅐ NO to form peroxynitrite (ONOO Ϫ ) accounts for removal of a proportion of ⅐ NO. However, this is by no means the only mechanism for ⅐ NO removal because it is incompletely restored by O 2 . scavengers (7). Nitric oxide consumption by bacterial flavohemoglobins forms NO 3 Ϫ via reaction with the oxy form (8 -10) and is a proposed defense against "nitrosative stress." Recently, rabbit and human 15-lipoxygenases were also found to catalytically consume ⅐ NO, through reaction with an en...

show abstract

Direct Measurement of Nitric Oxide Production in Platelets: Relationship with Cytosolic Ca2+ Concentration

Cited by 78 publications

References 0 publications

Platelet-Derived Nitric Oxide and Coronary Risk Factors

Platelet-Derived Nitric Oxide and Coronary Risk Factors

Human platelet nitric oxide synthase activity: an optimized method

Catalytic Consumption of Nitric Oxide by Prostaglandin H Synthase-1 Regulates Platelet Function

Contact Info

Product

Resources

About