Platelet adhesion to human vascular endothelium is modulated by constitutive and cytokine induced nitric oxide

Radomski, Marek W.; Vallance, Patrick; Whitley, Guy; Foxwell, Neale; Moncada, Salvador

doi:10.1093/cvr/27.7.1380

Cited by 221 publications

(99 citation statements)

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“…NADH and NADPH oxidase activity was measured according to the method described by Rajagopalan et al, 25 who demonstrated that this assay specifically measures NAD(P)H oxidase-generated superoxide. Briefly, platelets were homogenized by freeze and thawing, as described above.…”

Section: Nadh/nadph Oxidase Activitymentioning

confidence: 99%

Platelet Nitric Oxide and Superoxide Release During the Development of Nitrate Tolerance

et al. 2002

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Background-The therapeutic benefits that accompany the continuous administration of organic nitrates are attenuated by the development of tolerance to the compounds. Altered superoxide production and NO bioavailability have been implicated in contributing to the development of tolerance, an effect that may be ameliorated by the administration of antioxidants. Methods and Results-We studied the effect of 3 days of continuous transdermal administration of nitroglycerin (NTG) (10 mg/24 hours) on platelet free radical (NO and superoxide anion [O 2 ·Ϫ ] activity) with and without coadministration of supplemental ascorbate (2.4 g/24 hours). NAD(P)H oxidase activity, nitric oxide synthase (NOS) activity, and cyclic guanosine monophosphate (cGMP) content were also assessed. Radial artery pressure pulse waveforms were used to track the hemodynamic actions of NTG. Three days of NTG/placebo was associated with a significant increase in platelet NO and O 2 ·Ϫ production from 1.0Ϯ1.17 to 2.52Ϯ0.88 pmol/10 8 platelets and 13.2Ϯ4.8 to 72.5Ϯ34.4 pmol/10

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Section: Nadh/nadph Oxidase Activitymentioning

confidence: 99%

Platelet Nitric Oxide and Superoxide Release During the Development of Nitrate Tolerance

et al. 2002

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“…Human tumour cell lines SW480, SW620, DLD-l AssaYs of NOS activit} NOS activity was determined by measuring the rate of conversion of L-[U-'4C]arginine to [U-14Clcitrulline by soluble cytosolic extracts of the cells (Radomski et al. 1993).…”

Section: Cell Linesmentioning

confidence: 99%

Human colon cancer cell lines show a diverse pattern of nitric oxide synthase gene expression and nitric oxide generation

Jenkins

Charles²,

Baylis³

et al. 1994

Br J Cancer

124

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S _nnuay A panel of human colonic adenocarcinoma cell lines was examined both for expression of mRNAs of the nitric oxide synthase (NOS) gene family and for evidence of enzymic activity based on citrulline and nitrite (NO,-) formation. Reverse transcription-polymerase chain reaction (RT-PCR). revealed that all lines (SW480. SW620. DLD-1 and WiDr) expressed mRNA for the Ca-+-dependent endothelial (e)NOS. while SW480 cells also expressed the Ca2'-dependent neuronal (n)NOS. The mRNA for the Ca'+-independent inducible (i)NOS was expressed both by cytokine-stimulated and by unstimulated SW480. SW620 and DLD-1 cells, but none was seen at any time in the WiDr cells. There was, however, little correlation between mRNA expression and enzynic activity based on citruUline and NO,-formation. Thus none of the cell lines exhibited measurable Ca'-dependent NOS activity, while Ca2'-independent NOS activity was seen in all but the WiDr cells. Furthermore. DLD-1 cells generated citrulline with resultant NO.-formation only after stimulation with lipopolysacchanrde (LPS) and or cytokines. while SW480 and SW620 did so constitutively. Thus RT-PCR studies indicate that tumour cells of similar epithelial origin display a diverse pattern of NOS gene family expression. and parallel biochemical studies clearly indicate that such expression does not always result in measurable enzymic activity leading to the generation of NO.

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“…NO is synthesized from conversion of L-arginine to L-citrulline by a family of NO synthases (NOS), which include constitutive and inducible isoforms (Moncada et al, 1991). Basal release of NO by endothelial cells contributes to the maintenance of normal vasodilatory tone and thromboresistance (Radomski et al, 1987(Radomski et al, , 1993. Previously, Shultz and Raij (1992) demonstrated that rats given a low dose of endotoxin exhibit a marked increase in the urinary excretion of NO metabolites and no evidence of glomerular thrombosis.…”

mentioning

confidence: 99%

Down-Regulation of Renal Endothelial Nitric Oxide Synthase Expression in Experimental Glomerular Thrombotic Microangiopathy

Zhou

Lászik

et al. 2000

Laboratory Investigation

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SUMMARY:Infection with certain strains of Escherichia coli and endotoxemia results in renal glomerular thrombotic microangiopathy (TMA) characterized by endothelial swelling and prominent glomerular microthrombus formation. Nitric oxide (NO) is an endogenous biologic modulator with diverse physiologic functions including vasodilation and inhibition of platelet adhesion and aggregation. NO is synthesized from conversion of L-arginine to L-citrulline by a family of NO synthases (NOS), which include constitutive and inducible isoforms. Indirect evidence supports the hypothesis that TMA is associated with depressed intrarenal NO production. However, the effect of TMA on renal tissue NOS expression has not been fully elucidated. We studied rats with TMA induced by iv bolus injection of high dose (20 mg/kg) E. coli endotoxin. Subgroups of six animals each were sacrificed before or at 30, 90, 180, 360, and 720 minutes after the administration of endotoxin. Renal histology and tissue expression of endothelial and inducible nitric oxide synthases (eNOS and iNOS) were examined. Additionally, we examined the effect of endotoxin on glomerular NO production, and eNOS and iNOS protein expression in vitro. Glomerular capillary thrombosis developed by 180 minutes after endotoxin administration in approximately half of the animals. The glomeruli without thrombotic lesions apparent by light microscopy disclosed early signs of TMA characterized by endothelial swelling, platelet accumulation/adhesion, and patchy fibrinogen deposition. These morphologic changes were associated with a marked reduction of renal tissue eNOS expression beyond 180 minutes after the endotoxin administration. The fall in eNOS expression was coupled with a significant rise in iNOS protein abundance, which was expressed largely by glomerular circulating neutrophils and endothelial cells, peritubular vascular endothelium, and collecting ducts of cortex and medulla. In vitro incubation of isolated glomeruli with endotoxin also resulted in a marked reduction in eNOS expression and a significant rise in iNOS content. Administration of E. coli endotoxin leads to a sustained fall in renal eNOS expression both in vivo and in vitro. The associated decline in intrarenal endothelial NO production/availability may result in renal vasoconstriction and a hypercoagulative state, which may contribute to the pathogenesis of endotoxin-induced TMA. (Lab Invest 2000, 80:1079-1087.

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Platelet adhesion to human vascular endothelium is modulated by constitutive and cytokine induced nitric oxide

Cited by 221 publications

References 0 publications

Platelet Nitric Oxide and Superoxide Release During the Development of Nitrate Tolerance

Platelet Nitric Oxide and Superoxide Release During the Development of Nitrate Tolerance

Human colon cancer cell lines show a diverse pattern of nitric oxide synthase gene expression and nitric oxide generation

Down-Regulation of Renal Endothelial Nitric Oxide Synthase Expression in Experimental Glomerular Thrombotic Microangiopathy

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