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1.
The influences of experimental hypercholesterolemia in the rabbit on platelet-vessel wall interactions have been studied by evaluating the aggregatory response of platelet rich plasma (PRP) to arachidonic acid (AA) stimulation and levels of 6-keto-PGF1α in PRP from normal (N) and hypercholesterolemic (HC) animals prior and after perfusion through the corresponding aortas. In addition, the responses of N PRP to aggregation after perfusion through HC aortas and those of HC PRP perfused through N aortas, and the platelet response to the inhibitors effect of exogenous prostocyclin have been evaluated. The data indicate that in HC rabbits, on one side platelets aew hyperreactive to AA and less sensitive to the inhibitory activity of prostocyclin and, on the other, the antiaggregatory activity and prostacyclin production of vessel walls is higher, suggesting compensatory mechanisms in the haemostatic balance. 相似文献
2.
C Galli A Petroni A Socini E Agradi C Colombo G C Folco E Tremoli 《Prostaglandins》1981,22(5):703-713
An experimental model for the study of platelet-vessel wall interactions has been developed, based on perfusion of rat platelet rich plasma (PRP) through isolated rat aortas. In the perfused PRP, platelet aggregation was inhibited and levels of 6 Keto PGF1 alpha and cAMP were elevated over the values found in non perfused PRP. When PPP or buffer were perfused through the isolated artery, elevations of 6 Keto PGF1 alpha levels in the perfusate were smaller (in perfused PPP) or of shorter duration (in both perfused PPP and buffer). The presence of platelets in the perfusion fluid thus enhanced the formation of Prostacyclin by the arterial wall. Levels of 6 Keto PGF1 alpha in PRP obtained from aspirin-treated animals and in PRP from normal animals, both perfused through normal aortas, were the same, and also levels of the above metabolite in normal PRP perfused through aortas of aspirin-treated animals did not differ from those found in non perfused PRP. It is concluded, from these data, that PRP does not stimulate PGI2 formation in perfused aortas by providing cyclic endoperoxides. The experimental model developed allows the study of interactions between normal platelets and aortas from experimentally treated animals or viceversa. 相似文献
3.
C. Galli A. Petroni A. Socini E. Agradi C. Colombo G.C. Folco E. Tremoli 《Prostaglandins & other lipid mediators》1981,22(5):703-713
An experimental model for the study of platelet-vessel wall interactions has been developed, based on perfusion of rat platelet-rich plasma (PRP) through isolated rat aortas. In the perfused PRP, platelet aggregation was inhibited and levels of 6 Keto PGF1α and cAMP were elevated over the values found in non perfused PRP. When PPP or buffer were perfused through the isolated artery, elevations of 6 Keto PGF1α levels in the perfusate were smaller (in perfused PPP) or of shorter duration (in both perfused PPP and buffer). The presence of platelets in the perfusion fluids thus enhanced the formation of Prostacyclin by the arterial wall. Levels of 6 Keto PGF1α in PRP obtained from aspirin-treated animals and in PRP from normal animals, both perfused through normal aortas, were the same, and also levels of the above metabolite in normal PRP perfused through aortas of aspirin-treated animals did not differ from those found in non perfused PRP. It is concluded, from these data, that PRP does not stimulate PGI2 formation in perfused aortas by providing cyclic endoperoxides. The experimental model developed allows the study of interactions between normal platelets and aortas from experimentally treated animals or viceversa. 相似文献
4.
Sex differences in eicosanoid production in platelets and vessel walls have been studied in control and n-6 fatty acid supplemented rats. In platelet rich plasma (PRP) of control female rats, arachidonic acid (AA) levels in phospholipids (PL), thromboxane B2 (TxB2) formation following collagen stimulation and aggregatory responses to collagen were higher than in PRP of male rats. 6 keto PGF1α release from PRP-perfused isolated aortas were the same for both sexes, but the antiaggregatory activity of the wall was higher in males than in females, in association with a greater sensitivity of male platelets to prostacyclin.The administration of n-6 fatty acid supplements increased AA level in PL, TxB2 production and aggregation only in male platelets. Production of 6 keto PGF1α and the antiaggregatory activity of aortic walls were reduced after dietary treatment in males, but biochemical and functional parameters were not correlated in females.The results indicate complex sex-related differences in fatty acid metabolism and eicosanoid production, and in responses to n-6 dietary fatty acids in platelets and the vascular system in the rat. 相似文献
5.
Srihirun S Sriwantana T Unchern S Kittikool D Noulsri E Pattanapanyasat K Fucharoen S Piknova B Schechter AN Sibmooh N 《PloS one》2012,7(1):e30380
BACKGROUND: Nitrite is a nitric oxide (NO) metabolite in tissues and blood, which can be converted to NO under hypoxia to facilitate tissue perfusion. Although nitrite is known to cause vasodilation following its reduction to NO, the effect of nitrite on platelet activity remains unclear. In this study, the effect of nitrite and nitrite+erythrocytes, with and without deoxygenation, on platelet activity was investigated. METHODOLOGY/FINDING: Platelet aggregation was studied in platelet-rich plasma (PRP) and PRP+erythrocytes by turbidimetric and impedance aggregometry, respectively. In PRP, DEANONOate inhibited platelet aggregation induced by ADP while nitrite had no effect on platelets. In PRP+erythrocytes, the inhibitory effect of DEANONOate on platelets decreased whereas nitrite at physiologic concentration (0.1 μM) inhibited platelet aggregation and ATP release. The effect of nitrite+erythrocytes on platelets was abrogated by C-PTIO (a membrane-impermeable NO scavenger), suggesting an NO-mediated action. Furthermore, deoxygenation enhanced the effect of nitrite as observed from a decrease of P-selectin expression and increase of the cGMP levels in platelets. The ADP-induced platelet aggregation in whole blood showed inverse correlations with the nitrite levels in whole blood and erythrocytes. CONCLUSION: Nitrite alone at physiological levels has no effect on platelets in plasma. Nitrite in the presence of erythrocytes inhibits platelets through its reduction to NO, which is promoted by deoxygenation. Nitrite may have role in modulating platelet activity in the circulation, especially during hypoxia. 相似文献
6.
M.F. Gimeno L. Sterin-Borda E.S. Borda M.A. Lazzari A.L. Gimeno 《Prostaglandins & other lipid mediators》1980,19(6):907-916
Prostacyclin (PGI2) incubated in Human Platelet Rich Plasma (PRP); in Platelet Poor Plasma (PPP) or in Krebs-Ringer-Bicarbonate (KRB) during different periods of time on contractions of bovine coronary arteries and on the ADP platelet aggregative capacity of human PRP, were explored. It was documented that incubates in PRP or in PPP retain an antiaggregatory activity at higher levels and during a longer time than in KRB. On the other hand, PGI2 incubates in KRB exhibited only a relaxing activity on isolated bovine coronary arteries, whereas when incubated in PRP or in PPP presented a biphasic influence. The initial effects (evoked by incubates of 30 minutes) were distinctly relaxing but those obtained with later incubates (60–150 minutes) stimulated clearly the resting basal tone of the arteries. The possibility that the human plasma might have an enzyme(s) able to transform prostacyclin into a more stable material with human antiaggregatory platelet function and bovine coronary contracting capacity is discussed. 相似文献
7.
《Prostaglandins and medicine》1981,6(1):51-63
In the present study we have investigated the effect of Amrinone on the hemodynamics, platelet counts, prostacyclin and thromboxane synthesis and platelet function. Results show that infusion of the drug increased the heart rate and lowered left atrial, aortic and pulmonary artery pressures within five minutes after a single bolus injection of 2 mg/kg IV dose. Platelet counts made from the blood obtained from anesthetized dogs after the drug infusion showed severe loss of platelets. However, infusion of a similar dose in awake dogs showed no such detrimental effect on platelets. Examination of formalin fixed blood for aggregates showed no more clumps in the treated samples than in the control. Platelets obtained from canine blood drawn at 30 minutes post infusion of the drug showed no aggregatory response to arachidonate. However, the response of these platelets to ADP was quite normal. Amrinone infusion had no inhibitory effect on the ability of vascular tissue to convert arachidonic acid to prostacyclin. Similarly, no inhibitory action could be observed on platelet cyclo-oxygenase activity at this concentration (2 mg/kg). In vitro studies on human platelets showed significant inhibition of cyclo-oxygenase at high concentrations (0.5 mg/ml). Therefore it is unlikely that the drug caused inhibition of the platelet response to arachidonate by the inhibition of prostaglandin synthesis during infusion, as the dose used was quite low (2 mg/kg) compared to what is required for the inhibition of cyclo-oxygenase. 相似文献
8.
Effects of estradiol on the metabolism of arachidonic acid by aortas and platelets in rats 总被引:1,自引:0,他引:1
We have previously reported that estradiol treatment stimulates prostacyclin production by cultured rat aortic smooth muscle cells, through the stimulation of fatty acid cyclooxygenase and prostacyclin synthetase activities. In order to see whether estradiol stimulates the fatty acid cyclooxygenase activity in platelets, intact rats were treated with estradiol, and thromboxane biosynthesis in platelets and prostacyclin production by aortas were investigated. Estradiol significantly stimulates prostacyclin production by aortas. However, no significant effect on thromboxane biosynthesis in platelets is observed. Our present results support the idea that estradiol would be a protective hormone in atherosclerotic heart disease. 相似文献
9.
《Prostaglandins and medicine》1981,6(5):473-483
The effects of 6-keto-PGE1 on aggregatory responses to arachidonic acid (AA), adenosine diphosphate (ADP) and collagen were studied in human platelet-rich plasma (PRP). In addition, experiments were carried out to determine if these effects correlate with changes in platelet cyclic AMP and cyclic GMP levels. 6-Keto-PGE1 incubated in PRP produced dose-related increases in platelet cyclic AMP levels whereas platelet cyclic GMP levels were unchanged. Control aggregations induced by AA and ADP did not alter cyclic AMP and cyclic GMP levels whereas control aggregations induced by collagen elevated cyclic GMP levels while cyclic AMP levels were unchanged. 6-Keto-PGE1 produced a dose-dependent inhibition of platelet aggregation induced by AA, ADP and collagen and this inhibition correlated with a dose-related increase in cyclic AMP levels. Since 6-keto-PGE1 does not consistently alter cyclic GMP levels in human PRP, the present data support previous studies suggesting that 6-keto-PGE1 produces inhibition of platelet aggregation through the stimulation of cyclic AMP accumulation. 相似文献
10.
M Kh Tur'ianov K D Lomazova L V Kazanskaia Z V Chumakova A M Poliakova 《Biulleten' eksperimental'no? biologii i meditsiny》1983,96(9):33-35
The platelet aggregation reaction was used to assess the influence of arachidonic acid (AA), endotoxin (E) S. typhimurium and ADP on platelet aggregation properties. All the three substances induced platelet aggregation. A higher degree of aggregation was attained by the application of E combined with AA and ADP as compared with the effects produced by E and ADP alone. Prolonged incubation of platelet-rich plasma (PRP) samples with E led to an essential decrease of the aggregation degree on ADP addition. Incubation of PRP samples with E and ADP did not evoke any analogous decrease in the platelet aggregation degree. The data obtained indicate that AA stimulates platelet aggregation induced by E and ADP. 相似文献
11.
The developmental pattern of fetal and neonatal rabbit lungs to generate an antiaggregatory compound from arachidonic acid (AA) was studied in isolated rabbit lungs, which were perfused with Krebs bicarbonate buffer. The antiaggregatory effect of the nonrecirculating perfussion effluent was tested by adding a small portion of the effluent to human platelet rich plasma (PRP) in a Born-type aggregometer before the aggregation was induced by ADP. The production of an antiaggregatory compound was minimal, when exogenous AA was not infused into the pulmonary circulation. When arachidonate (40 nmol/min) was infused into the pulmonary circulation of rabbits which were 1 day or 1 week old, the perfusion effluent significantly inhibited the ADP induced aggregation of PRP. Perfused lungs from fetal rabbits (gestation age 28–31 days) formed also an antiaggregatory compound fro AA, but the antiaggregatory effect was not as great as 1 day after birth. It seems that neonatal rabbit lungs metabolize AA more to an antiaggregatory compound than late fetal lungs. The fact that the AA induced production of an antiaggregatory compound is inhibited by simultaneous infusion of indomethacin favours the hypothesis that this antiaggregatory compound could he PGI2. 相似文献
12.
《Prostaglandins, Leukotrienes and Medicine》1982,8(2):125-132
5-methoxy-2-methyl-3-indole acetic acid (5MIAA) is a metabolite and alkali hydrolysis product of indomethacin. This indole derivative was previously found to be an effective in vivo inhibitor of platelet aggregation in an experimental model of microvascular injury in the mouse. In a standard aggregometer assay, the in vitro inhibitory action of 5MIAA was weak and failed to explain its in vivo effect. The present study employed two assay systems testing the capacity of 5MIAA to increase the aggregate inhibiting activity of the aorta. In one series of experiments the aorta, the drug and platelet rich plasma were incubated together, and in another series aliquots of aortic incubation media were transferred to PRP. Both types of study showed that 5MIAA interacts with the aorta and with a substance(s) produced by aortic wall to markedly inhibit aggregation stimulated by arachidonic acid. Thus, when 100μg/ml of 5MIAA, which by itself had a negligible effect on aggregation, was added to a cuvette containing both aorta and PRP, the inhibitory effect of the aorta was enhanced three fold. The substance with which 5MIAA interacts was eliminated by cyclooxygenase inhibitors, but direct tests of 5MIAA's ability to potentiate the effect of prostacyclin were unsuccessful. 相似文献
13.
Although HHT accounts for approximately one third of the arachidonic acid (AA) metabolites produced by stimulated platelets, no well defined function has been attributed to this product. We report that HHT stimulates prostacyclin production by endothelial cells, and have identified the mechanism for this effect. In human umbilical venous endothelial cells, HHT (0.5 and 1 microM) stimulated prostacyclin (RIA for 6KPGF1 alpha) by 32 +/- 22% (1SD) and 42 +/- 38% (P less than 0.05 and less than 0.01). Similar changes were observed when the effect of HHT on exogenous [1-14C] AA metabolism in fetal bovine aortic endothelial cells (FBAECs) was studied. Kinetic analyses revealed that HHT affected vascular cyclooxygenase. HHT (1 microM) increased Vmax in test microsomes (706 +/- 21 pmol/mg/min, mean +/- 1SE) when compared to controls (529 +/- 20; P less than 0.02). No concomitant effect on Km was observed. A further effect of HHT on AA release from endothelial cell membrane phospholipids was noted. Prelabeling experiments revealed that HHT (1 microM) increased the ionophore stimulated release of AA from FBAECs (20952 +/- 555 cpm/well control mean +/- 1SE vs 25848 +/- 557 for paired HHT treated cells; P less than 0.05). The effect of HHT on platelet AA metabolism was next studied. Preincubation of washed platelets with HHT (1 microM) did not enhance thrombin or arachidonic acid induced platelet TXB2 formation. In platelets prelabelled with [1-14C]AA, HHT (1 microM) had no effect on AA release post thrombin stimulation. Conversion to cyclooxygenase metabolites was also not enhanced. HHT stimulates vascular prostacyclin without a concomitant effect on platelet AA metabolism. HHT may thus be an important local modulator of platelet plug formation. 相似文献
14.
Miceli M Alberti L Bennardini F Di Simplicio P Seghieri G Rao GH Franconi F 《Life sciences》2003,73(12):1557-1566
In vitro, high concentrations of ethanol (EtOH) reduce platelet aggregation. Less is known about the effect of low EtOH doses on platelet function in a selected human population of long-life abstainers and low moderate-wine drinkers to avoid rebound effect of EtOH on platelet aggregation. Results of our experiments suggest that moderate-wine drinkers have higher levels of high density lipoprotein (HDL) than long-life abstainers while fibrinogen levels are unchanged. Furthermore, platelets obtained from these individuals do not differ in their response when stimulated by agonists such as AA and collagen. The effect of in vitro exposure of low doses of EtOH has been studied in PRP and in washed platelets. EtOH (0.1-10 mM) inhibits platelet aggregation induced by collagen at its ED50 while is ineffective when aggregation was triggered by U-46619 and by 1 microM adenosine diphosphate (ADP). 5-10 mM EtOH partially reduces the second wave of aggregation induced by 3 microM ADP. 0.1-10 mM EtOH dose-dependently lowers the aggregation induced by AA at its ED50 but it is less effective at ED75 of AA. The antiaggregating effect of EtOH on aggregation induced by AA is unchanged by inhibitor of nitric oxide synthase. In addition, 10 mM EtOH reduces thromboxane (Tx) formation. In washed platelets, 1-10 mM EtOH partially inhibits platelet aggregation induced by thrombin. In washed resting platelets, 10 mM EtOH does not change the resting [Ca++]i while significantly reduces the increase in [Ca++]i triggered by AA. The results of ex vivo experiments have demonstrated that wine increases the HDL. However, this observation may or may not influence the response of platelets to agonists. Results of our studies demonstrate that low doses of alcohol reduces platelet function. 相似文献
15.
Role of platelet endothelial form of nitric oxide synthase in collagen-platelet interaction: regulation by phosphorylation 总被引:3,自引:0,他引:3
Different pathways have been reported to be involved in platelet-collagen interaction. We have reported that the platelet endothelial form of nitric oxide synthase (eNOS) and the platelet receptor for type I collagen, p65, are closely associated. But the controlling mechanism underlying the generation of nitric oxide (NO) by the eNOS has not been fully explored. In this investigation, Western blot analyses of time course samples with anti-phosphorylated tyrosine, and anti-serine/threonine showed a marked increase in serine/threonine phosphorylation of eNOS during type I collagen-induced platelet aggregation. Meanwhile, the eNOS activity measured by the conversion of [3H]-arginine to [3H]-citrulline is significantly decreased. Correlation of type I collagen-induced platelet aggregation and the activity of eNOS in the presence of the serine/threonine phosphatase inhibitor, okadiac acid and the tyrosine phosphatase inhibitor, vanadate were performed with PRP. Results show the decrease in eNOS activity by adding okadiac acid correlated with the inhibitory effect on platelet aggregation in a dose-dependent manner. On the other hand, vanadate significantly inhibits platelet aggregation and also inhibits eNOS activity when the concentration of vanadate is greater than 2 mM. These results suggest that phosphorylation of serine/threonine and tyrosine residues control the activity of eNOS through different mechanisms to affect collagen-induced platelet aggregation. 相似文献
16.
An antiserum was raised in rabbits using 5,6-dihydro prostacyclin, a stable analogue of prostacyclin, as the hapten, conjugated to bovine serum albumin. When added to platelet rich plasma the antiserum neutralised the inhibitory activity of prostacyclin, prostaglandin E1 and D2. The amount of antiserum required to neutralise completely a dose of prostacyclin giving 90-95% inhibition of ADP induced aggregation was 10-30 times less than that required for the other two prostaglandins. Small amounts of antiserum prevented the inhibitory activity of prostacyclin generated from endothelial cells in platelet rich plasma. 相似文献
17.
Prostacyclin (PGX) ( has been found to be a potent stimulator of cAMP accumulation in human platelet rich plasma (PRP), and a direct stimulator of platelet microsome adenylate cyclase. Prostacyclin is, on a molar basis, at least 10 times more potent a stimulator of cAMP accumulation in platelets than PGE1. The prostacyclin stimulation of platelet cAMP accumulation can be antagonized by the prostaglandin endoperoxide PGH2, and a PGH2-induced platelet aggregation is antagonized by prostacyclin. A model of platelet homeostasis is proposed that suggests platelet aggregation is controlled by a balance between the adenylate cyclase stimulating activity of prostacyclin, and the cAMP lowering activity of PGH2. 相似文献
18.
S. Bunting S. Moncada P. Reed J.A. Salmon J.R. Vane 《Prostaglandins & other lipid mediators》1978,15(4):565-573
An antiserum was raised in rabbits using 5,6-dihydro prostacyclin, a stable analogue of prostacyclin, as the hapten, conjugated to bovine serum albumin. When added to platelet rich plasma the antiserum neutralised the inhibitory activity of prostacyclin, prostaglandin E1 and D2. The amount of antiserum required to neutralise completely a dose of prostacyclin giving 90–95% inhibition of ADP induced aggregation was 10–30 times less than that required for the other two prostaglandins. Small amounts of antiserum prevented the inhibitory activity of prostacyclin generated from endothelial cells in platelet rich plasma. 相似文献
19.
Onodera M Morita Mano Y Murota S 《Prostaglandins, leukotrienes, and essential fatty acids》2000,62(3):161-167
A number of studies have demonstrated that prostacyclin and nitric oxide (NO) regulate blood pressure, blood flow and platelet aggregation. In this paper, we have examined the possible relationship between NO and prostaglandin endoperoxide H synthase (PGHS)-1 and -2 activities in cultured bovine aortic endothelial cells. In the non-activated condition endothelial cells expressed PGHS-1 activity alone. When these cells were pretreated with aspirin to inactivate their PGHS-1 and then activated by serum and phorbol ester (TPA) for 6 h, the cells expressed PGHS-2 activity alone. The PGHS activity was assessed by the generation of 6-ketoprostaglandin F1alpha (6-ketoPGF1alpha), a stable metabolite of prostacyclin, after the treatment of these cells with arachidonic acid. The simultaneous addition of NOC-7, a NO donor, with arachidonic acid did not affect the production of 6-ketoPGF1alpha in PGHS-1 expressed cells, but attenuated it in PGHS-2-expressed cells. The inhibitory effect of NOC-7 on PGHS-2 activity was dose dependent, and the different effects of NOC-7 on the activities of PGHS isozymes were also observed in other NO donors. To confirm the different effect of NO on PGHS isozymes demonstrated in the cultured endothelial cells, we carried out an ex vivo perfusion assay in aorta isolated from normal and lipopolysaccharide (LPS)-treated rats. In the aortae isolated from normal rats, where dominant expression of PGHS-1 was expected, the NO donor did not affect the PGHS activity, while in aortae isolated from LPS-treated rats, where PGHS-2 was dominantly expressed, the NO donor dramatically inhibited the PGHS activity, suggesting that NO suppressed PGHS-2 activity alone. The inhibitory effect of NO on PGHS-2 activity was not mediated by cyclic GMP (cGMP), since (a) methylene blue, an inhibitor of soluble guanylate cyclase did not abolish the inhibitory effect of the NO donor on PGHS-2 activity, and (b) 8-Br-cGMP, a permeable cGMP analogue, failed to mimic the effect of NO donors. These data suggest that the effect of NO on prostacyclin production in endothelial cells was dependent on the expression rate of PGHS-1 and PGHS-2 in the cells. 相似文献
20.
BACKGROUND: Although cross-talks between platelets and other blood cells are important in vivo, laboratory platelet aggregation tests have been performed mainly with the use of platelet-rich plasma (PRP) as samples. Methods that enable an efficient and sensitive detection of platelet aggregates in whole blood are being developed. METHODS: A flow cytometer equipped with an imaging device, the flow imaging cytometer 2 (FIC2), was used to detect platelet aggregates in whole blood. RESULTS: The FIC2 provides a resolution that is high enough to differentiate platelet aggregates from single platelets or other blood cells. Epinephrine elicited platelet aggregate formation in hirudin plus argatroban-treated whole blood, but not in PRP. The reconstitution study revealed that a small amount of adenosine diphosphate (ADP) from erythrocytes may play an important role in epinephrine-induced platelet aggregation (in whole blood), through mediation of P2Y1 receptors. When the inhibitory effect of beraprost, an antiplatelet agent, on platelet aggregation was assessed, analysis of whole blood samples with FIC2 proved to be the most sensitive among the methods available. CONCLUSIONS: FIC2 is a promising device for detection of platelet aggregates in whole blood, with wide basic and clinical applications. 相似文献