Aspirin acetylates nitric oxide synthase type 3 in platelets thereby increasing its activity

Xie, Liping; Liu, Zhen; Queen, Lindsay; Jackson, Graham; Ji, Yong; Ferro, Albert

doi:10.1093/cvr/cvp120

Cited by 36 publications

(20 citation statements)

References 27 publications

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“…The activity of NOS, apparently, is closely related to the function of COX. It has been proposed that, besides the inhibition of COX in platelets, aspirin could activate NOS by a mechanism that is independent of COX inhibition; aspirin acetylates NOS enhancing its activity and decreasing phosphorylation [15][16][17]. It is known that superoxide and nitric oxide are readily produced in cells.…”

Section: Discussionmentioning

confidence: 99%

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Lactate is a possible mediator of the glucose effect on platelet inhibition

2013

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Glucose has been found to impair the inhibition of platelets with aspirin and alter the basal activity of nitric oxide synthase (NOS) in platelets. The aim of this work was to study the effects of glucose on the inhibitory pathways in activated platelets. A short-term incubation of glucose impaired the inhibition of platelet aggregation induced by agents activating an NOS-dependent pathway, such as l-arginine, adenosine and α-tocopherol. However, glucose had no effect on the inhibition induced by iloprost and BW245C, agents that activate the cyclic adenosine monophosphate (cAMP) signaling pathway. Potassium lactate attenuated the effects of the same inhibitors as glucose did. The inhibitors of glucose transport prevented the effect of glucose. Dichloroacetate, known to prevent the conversion of pyruvate to lactate and to decrease lactate in platelets, significantly attenuated the effect of glucose in platelets. The data support the suggestion that the effect of glucose on the inhibition of platelets by agents activating an NOS-dependent pathway is mediated by glucose metabolite lactate.

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Section: Discussionmentioning

confidence: 99%

“…A shortterm exposure of platelets to glucose also impairs the inhibitory effect of aspirin on platelets [11][12][13]. The activity of NOS and that of cyclooxygenase (COX) in platelet preparations are closely related [14][15][16][17]. Recently we proposed that lactate might mediate the effect of glucose [13].…”

Section: Introductionmentioning

confidence: 99%

Lactate is a possible mediator of the glucose effect on platelet inhibition

2013

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“…Examples include creatine kinase, commonly used as a diagnostic biomarker of MI, and aspirin, b-blockers, and angiotensin-converting enzyme (ACE) inhibitors, each used as standard therapies and known to alter phosphorylation. Specifically, aspirin, a cyclooxygenase (COX)1/2 inhibitor, alters STAT signaling, nitric oxide synthase (NOS) phosphorylation, and NFjB inhibition [13,64]. Beta-adrenoceptors, inhibited by b-blockers, are coupled to Gs-proteins that form cyclic adenosine monophosphate (cAMP) to stimulate PKA [52], and ACE inhibitors increase Akt and protein kinase C (PKC) phosphorylation, while inhibiting phosphorylation of MAPKs, IKKs, and mammalian target of rapamycin (mTOR) (a PI3K family member) [6].…”

Section: Heart Failure and Myocardial Infarctionmentioning

confidence: 99%

Phosphorylation mechanisms in intensive care medicine

Martin

Ranieri

2010

Intensive Care Med

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“…28,29 The platelet suspension was incubated at 37 1C in the presence of L-[ 3 H]arginine (1 mmol l À1 ) for 15 min. All reactions were stopped by rapid centrifugation (2000 g, 15 s), followed by two washes with Krebs buffer.…”

Section: Measurement Of Platelet Nos Activitymentioning

confidence: 99%

Characterization of the L-arginine–NO–cGMP pathway in spontaneously hypertensive rat platelets: the effects of pregnancy

et al. 2010

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Nitric oxide (NO) is a short-lived intercellular messenger that provides an efficient vascular regulatory mechanism to support homeostasis and prevent thrombosis. Endothelial dysfunction and reduced NO bioavailability have a central role in hypertension associated with pregnancy. The purpose of this study was to investigate the impact of pregnancy on the L-arginine-NO-cGMP pathway in platelets and its correlation to platelet function and blood pressure in normotensive rats and spontaneously hypertensive rats (SHRs). Platelets were obtained from blood on the 20th day of pregnancy from female SHRs (SHR-P) and normotensive controls (P) or age-matched nonpregnant rats (SHR-NP and NP). Intraplatelet NO synthase (NOS) activity was reduced in P compared to NP, despite unchanged L-arginine influx. The expression levels of endothelial NOS (eNOS) and inducible NOS (iNOS) were diminished during pregnancy in normotensive rats. Paradoxically, cyclic guanosine monophosphate (cGMP) levels were similar between NP and P, as were phosphodiesterase type 5 (PDE5) expression and platelet aggregation induced by adenosine diphosphate. In SHRs, L-arginine influx was reduced in SHR-P compared to SHR-NP. SHR-P exhibited impaired NOS activity and reduced iNOS expression compared with SHR-NP. Soluble guanylyl cyclase and PDE5 expression in platelets were lower in SHR-P than in SHR-NP, whereas no differences were noted between groups with respect to cGMP levels. However, increased levels of cGMP were observed in SHR-P compared to normotensive groups and platelet aggregability remained unaltered. In conclusion, these observations prompted the hypothesis that normal platelet aggregation in pregnant SHRs may be related to a reduction in PDE5 expression and consequently the maintenance of cGMP levels, independently of reduced platelet NO bioavailability.

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Aspirin acetylates nitric oxide synthase type 3 in platelets thereby increasing its activity

Cited by 36 publications

References 27 publications

Lactate is a possible mediator of the glucose effect on platelet inhibition

Lactate is a possible mediator of the glucose effect on platelet inhibition

Phosphorylation mechanisms in intensive care medicine

Characterization of the L-arginine–NO–cGMP pathway in spontaneously hypertensive rat platelets: the effects of pregnancy

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