Effect of bradykinin and thrombin on prostacyclin synthesis in endothelial cells from calf and pig aorta and human umbilical cord vein

Hong, Suchen L.

doi:10.1016/0049-3848(80)90201-7

Cited by 241 publications

(75 citation statements)

References 7 publications

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“…The methyl ester, trimethylsilyl ether derivative of peak II gave prominent ions at 225 (base peak), 316 (M'-90), 335 (M+-71), 375 (M+-31), 391 (M+-15), and the molecular ion at 406. This mass spectrum is identical to the published mass spectrum of the methyl ester, trimethylsilyl ether derivative of 15 figure 4, A). Peaks I, II, III, and IV were found to have RP-HPLC retention times (14.5 to 21.0 min) analogous to those of dihydroxy arachidonate molecules.…”

Section: Resultssupporting

confidence: 81%

Evidence for 15-HETE synthesis by human umbilical vein endothelial cells.

Gorman¹,

Oglesby²,

Bundy³

et al. 1985

Circulation

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Incubation of cultured human umbilical vein endothelial cells with -4C]-arachidonic acid, followed by RP-HPLC analysis, resulted in the appearance of two principal radioactive products besides 6-keto-PGF,. The first peak was HHT, a hydrolysis product of the prostaglandin endoperoxide. The second peak was esterified, converted to the trimethylsilyl ether derivative, and analyzed by GC/MS and was shown to be the lipoxygenase product 1 5-HETE. Stimulation of endothelial cells with thrombin enhanced 15-HETE synthesis from arachidonate. Subsequent experiments showed that 5-HETE and 12-HETE were also synthesized by endothelial cells, but no evidence of leukotriene synthesis was found. Incubation of the 15-HETE precursor 1 5-HPETE with endothelial cells resulted in the formation of four distinct ultraviolet light-absorbing peaks. Ultraviolet and GC/MS analysis showed these peaks to be 8, 15-diHETEs that differed only in their hydroxyl configuration and cis-trans double-bond geometry. Formation of 8,15-diHETE molecules suggests the prior formation of the unstable epoxide molecule 14,15-LTA4 or an attack at C-10 of 15-HPETE by an enzyme with mechanistic features in common with a 12-lipoxygenase. The observation that endothelial cells can synthesize both 15-HETE and 8,15-diHETE molecules suggests that this cell type contains both a 15-lipoxygenase and a system that can synthesize 14,15-LTA4. Circulation 72, No. 4, 708-712, 1985. PG12* is the principal prostaglandin biosynthesized by cultured human umbilical vein endothelial cells in response to thrombin, histamine, A-23 187, trypsin, and ATP. LTC4 and LTD4 were shown to stimulate PGI2 biosynthesis in human endothelial cells, and agonist-specific desensitization to LTC4 was also observed.6. 7 Although leukotrienes are known to stimulate prostaglandin biosynthesis in endothelial cells, no physical evidence of arachidonate lipoxygenation by endothelial cells has appeared. In this report we present evidence that human umbilical vein endothelial cells do contain a 15-lipoxygenase.

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Section: Resultssupporting

confidence: 81%

Evidence for 15-HETE synthesis by human umbilical vein endothelial cells.

Gorman¹,

Oglesby²,

Bundy³

et al. 1985

Circulation

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“…However, even if this effect does apply in vivo, the discrepancy between the capacity of tissues to synthesize eicosanoids and their actual production rates in vivo35 would still theoretically permit an increase in prostacyclin formation in vivo in response to physical and/or chemical stimuli, despite a reduction in the capacity to generate this eicosanoid.2`In the present study, selective inhibition of platelet thromboxane formation resulted in a tendency for prostacyclin metabolite excretion to decline in the chronic smokers. However, the diference between the groups was not completely abolished, suggesting that other factors, such as platelet derived mediators,52 3 thrombin, 54 The difference in the ex vivo aggregation studies between the groups might then be explained if the effects of cigarette smoking on platelet function in vivo resulted primarily from vascular damage65 66 rather than a primary effect on platelets themselves. For example, in experimental animals, repeated vascular damage will shorten platelet survival in the absence of thrombosis,67 whereas intravascular thrombosis that is unassociated with extensive vascular damage does not result in a shortened platelet survival.68 It has been suggested that such "battered platelets" that have undergone reversible contact interactions in vivo might be so modified as to be more rapidly cleared from the circulation69; they might also be less susceptible to aggregating agonists ex vivo.…”

Section: Discussionmentioning

confidence: 98%

Biochemical evidence of a chronic abnormality in platelet and vascular function in healthy individuals who smoke cigarettes.

Nowak¹,

Murray²,

Oates³

et al. 1987

Circulation

333

140

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Cigarette smoking is associated with increased mortality from cardiovascular disease that declines after cessation. This study extends the evidence regarding the effects of chronic smoking on platelets and the vessel wall in vivo. Excretion of a major urinary thromboxane metabolite, 2,3-dinor-thromboxane B2, is significantly (p < .01) elevated in apparently healthy chronic smokers (20 cigarettes daily) compared with that in nonsmoking control subjects. This difference in excretion of 2,3-dinor-thromboxane B2 was abolished by the administration of 20 mg aspirin twice daily, a dose shown to selectively inhibit platelet cyclooxygenase. After aspirin, the return of the excretion of 2,3-dinor-thromboxane B2 to pretreatment levels paralleled the recovery of platelet cyclooxygenase. These findings indicate that excessive thromboxane A2 generation in chronic smokers predominantly derives from platelets. The urinary excretion of the prostacyclin metabolite 2,3-dinor-6-keto-prostaglandin F,,, also is increased during chronic cigarette smoking, as is the case with other diseases associated with accelerated interaction of platelets with the vessel wall. We have found evidence of platelet and vascular dysfunction in vivo in chronic cigarette smokers before the manifestation of overt cardiovascular disease. The results would also be consistent with the hypothesis that in chronic smokers, the platelet defect is largely reflective of smoking-induced vascular injury.

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“…We initially hypothesized that since BK is such a potent stimulator of NO formation and prostacyclin and tPA release, the absence of the constitutively expressed BK B2 receptor would make these animals prothrombotic. [11][12][13] The finding that the BKB2R Ϫ/Ϫ mice were protected from thrombosis indicated that another overriding mechanism (or mechanisms) is occurring.…”

Section: Discussionmentioning

confidence: 99%

“…[11][12][13] Contrary to that hypothesis, BKB2R Ϫ/Ϫ mice had delayed time to vessel occlusion (78 Ϯ 6.7 minutes, n ϭ 9 [mean Ϯ SEM] vs 31 Ϯ 2.7 minutes in B6129SF2/J controls, n ϭ 19; P Ͻ .001) when carotid artery injury was instituted on the Rose Bengal model for thrombosis, an endothelial-cell photochemical injury model due to local free radicals release (Figure 1). Furthermore, BKB2R Ϫ/Ϫ mice had a mean tail bleeding time of 135 Ϯ 11 seconds (mean Ϯ SEM, n ϭ 8) whereas control animals had a bleeding time of 81 Ϯ 4 seconds (n ϭ 8) (P Ͻ .001).…”

Section: Determination Of Thrombotic Risk In Bkb2r ؊/؊ Micementioning

confidence: 99%

“…5,9,10 BK by binding to the constitutive bradykinin B2 receptor (BKB2R) in the intravascular compartment promotes blood flow through nitric oxide (NO) and prostacyclin formation and tissue plasminogen activator (tPA) liberation. [11][12][13] Single chain urokinase activation promotes plasmin formation. 10 Factor XII activation amplifies PK activation and BK liberation and modulates HK binding to endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

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