Endogenous levels of 15-keto-dihydro-prostaglandins in human plasma

Samuelsson, Bengt; Gréen, K.

doi:10.1016/0006-2944(74)90127-6

Cited by 78 publications

(12 citation statements)

References 18 publications

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“…This is distinct from evidence provided by methods which measure the capacity of isolated tissues to synthesize eicosanoids ex vivo. The measurement of urinary prostaglandin metabolites has been successfully applied to estimate endogenous prostanoid biosynthesis by several groups of workers (18)(19)(20) The results of the present study are in accord with previous observations that thromboxane generation is highly susceptible to aspirin inhibition (24)(25)(26) (15) and may thus largely reflect extrarenal endogenous prostacyclin bioAspirin, Prostacyclin, Thromboxane A2, and Platelets synthesis (27). Although 6-keto-PGFi, is recovered in urine after systemic administration of prostacyclin (15) it may largely reflect renal prostacyclin synthesis under physiological conditions (26), although this has been disputed (28).…”

Section: Discussionmentioning

confidence: 99%

Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man.

FitzGerald¹,

Oates²,

Hawiger³

et al. 1983

J. Clin. Invest.

642

268

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A B S T R A C T To assess the pharmacologic effects of aspirin on endogenous prostacyclin and thromboxane biosynthesis, 2,3-dinor-6-keto PGFia (PGI-M) and 2,3-dinor-thromboxane B2 (Tx-M) were measured in urine by mass spectrometry during continuing administration of aspirin. To define the relationship of aspirin intake to endogenous prostacyclin biosynthesis, sequential urines were initially collected in individuals prior to, during, and subsequent to administration of aspirin. Despite inter-and intra-individual variations, PGI-M excretion was significantly reduced by aspirin. However, full mass spectral identification confirmed continuing prostacyclin biosynthesis during aspirin therapy. Recovery of prostacyclin biosynthesis was incomplete 5 d after drug administration was discontinued. To relate aspirin intake to indices of thromboxane biosynthesis and platelet function, volunteers received 20 mg aspirin daily followed by 2,600 mg aspirin daily, each dose for 7 d in sequential weeks. Increasing aspirin dosage inhibited Tx-M excretion from 70 to 98% of pretreatment control values; platelet TxB2 formation from 4.9 to 0.5% and further inhibited platelet function.An extended study was performed to relate aspirin intake to both thromboxane and prostacyclin genera- tion over a wide range of doses. Aspirin, in the range of 20 to 325 mg/d, resulted in a dose-dependent decline in both Tx-M and PGI-M excretion. At doses of 325-2,600 mg/d Tx-M excretion ranged from 5 to 3% of control values while PGI-M remained at 37-23% of control. 3 d after the last dose of aspirin (2,600 mg/ d) mean Tx-M excretion had returned to 85% of control, whereas mean PGI-M remained at 40% of predosing values. Although the platelet aggregation response (Tmax) to ADP ex vivo was inhibited during administration of the lower doses of aspirin the aggregation response returned to control values during the final two weeks of aspirin administration (1,300 and 2,600 mg aspirin/d) despite continued inhibition of thromboxane biosynthesis.These results suggest that although chronic administration of aspirin results in inhibition of endogenous thromboxane and prostacyclin biosynthesis over a wide dose range, inhibition of thromboxane biosynthesis is more selective at 20 than at 2,600 mg aspirin/d. However, despite this, inhibition of platelet function is not maximal at the lower aspirin dosage. Doses of aspirin in excess of 80 mg/d resulted in substantial inhibition of endogenous prostacyclin biosynthesis. Thus, it is unlikely that any dose of aspirin can maximally inhibit thromboxane generation without also reducing endogenous prostacyclin biosynthesis. These results also indicate that recovery of endogenous prostacyclin biosynthesis is delayed following aspirin administration and that the usual effects of aspirin on platelet function ex vivo may be obscured during chronic aspirin administration in man.

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Section: Discussionmentioning

confidence: 99%

Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man.

FitzGerald¹,

Oates²,

Hawiger³

et al. 1983

J. Clin. Invest.

642

268

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“…The difference between concentrations before and after treatment was not significant and the value after resolution was not significantly different from that of normal infants (42-0 (20.4)), or infants in the comparison group (33-5 (17)). These latter values do not differ from those reported for normal individuals by radioimmunoassay, gas chromatography and mass spectrometry,14 15 and with the calculated rate of prostaglandin F2 a synthesis in humans.15 The plasma prostaglandin metabolite concentration of the single infant in the comparison group (group V) who had pneumonia without wheezing was less than the lowest detectable concentration. To illustrate the group differences, plasma concentrations of the metabolite were converted to log values ( fig 1).…”

Section: Resultsmentioning

confidence: 69%

Increases in plasma concentrations of a prostaglandin metabolite in acute airway obstruction.

Skoner

Fireman

Davis

et al. 1989

Archives of Disease in Childhood

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SUMMARY Plasma concentrations of a stable prostaglandin F2 a metabolite were measured by radioimmunoassay during and after recovery from acute airway obstruction in 15 infants. Mean (SEM) metabolite concentrations (ng/l) in plasma obtained both before (1033 (418)) and after (1470 (413)) initial treatment for airway obstruction were significantly higher than those obtained from the same subjects after resolution of the obstruction-25-5 (6-6)-and those obtained from two comparison groups.

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“…It is unlikely that their main source is leakage of circulat ing PGs from retinal and choroidal blood vessels, as plama levels of PGE2 and prosta cyclin [20,21] are lower than vitreal levels observed in our detached eyes. Also, in long-standing RRD, the blood-retina bar rier remains intact, as demonstrated by us ing intravenous horseradish peroxidase [22], thus hindering possible leakage.…”

Section: Discussionmentioning

confidence: 70%

“…The involvement of PGE2 in various ocu lar diseases is well documented [4,5,[8][9][10][11][12][13]; it has been shown to have a mediatory role in the inflammatory process, causing polymor phonuclear cell chemotaxis, vasodilatation and increased permeability of blood vessels [1,2], Prostacyclin, generated by the vascu lar endothelium, is also involved in the in flammatory process, though to a lesser de gree [3], PGE2 and prostacyclin are the cyclo-oxy genase products of arachidonic acid [1][2][3], and their formation in the eye is initiated by various stimuli such as trauma, ischemia, nervous excitation and laser irradiation [13,[16][17][18][19], PGE2 produced by the retina is not stored but released into the vitreous [19], In disease-free subjects, vitreal PGE2 and pros tacyclin levels do not differ significantly from plasma levels [20,21],…”

Section: Discussionmentioning

confidence: 99%

Prostanoids in the Vitreous of Diabetic and Nondiabetic Human Eyes with Retinal Detachment

Naveh

Belkin²,

Ben-Chaim³

et al. 1990

Ophthalmic Res

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We measured prostaglandin E₂ (PGE₂) and prostacyclin levels in the vitreous bodies of 5 eyes of patients with diabetic retinopathy complicated by rhegmatogenous retinal detachment (RRD) and compared them with the corresponding levels in 9 nondiabetic eyes with the same condition as well as with 10 control eyes of deceased patients with no known ocular pathology. We also studied the effect of surgical retinal reattachment on vitreal PGE₂and prostacyclin levels in 4 eyes. Vitreal samples from both nondiabetic and diabetic eyes with RRD were obtained during vitrectomy, while samples from deceased subjects (controls) were obtained 2–6 h after death. Vitreal PGE₂ and prostacyclin levels in the control eyes approximated plasma levels (79.9 ± 20.5 and 124.5 ± 38.5 pg/ml, means ± SD, respectively), while RRD in the nondiabetic eyes was associated with increased levels of both PGE₂ and prostacyclin (3,170 ± 3,024 and 467 ± 283 pg/ml, respectively). In the diabetic eyes with diabetic retinopathy complicated by RRD, all of which underwent retinal photocoagulation, PGE₂ and prostacyclin levels were 2–4 times lower than those of the nondiabetic eyes with detached retina. Following surgical retinal reattachment, vitreal levels of both components in diabetics and nondiabetics showed a reduction suggesting that the surgical procedure for obtaining vitreal samples was not the cause for elevated prostaglandin levels in the eyes with detached retina. We showed that RRD is associated with an excessive accumulation of PGE₂ and prostacyclin in the vitreous, which is higher in nondiabetic than in diabetic eyes, indicating that diabetic retinopathy in laser-treated eyes might lead to reduced vitreal levels of these metabolites.

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Endogenous levels of 15-keto-dihydro-prostaglandins in human plasma

Cited by 78 publications

References 18 publications

Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man.

Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man.

Increases in plasma concentrations of a prostaglandin metabolite in acute airway obstruction.

Prostanoids in the Vitreous of Diabetic and Nondiabetic Human Eyes with Retinal Detachment

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