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At least 1,063 records · Page 59Linked to original sources
PubMed1992

Platelet aggregation in spontaneous hypertension: genetic determination and correlation analysis.

OBJECTIVE: Hyper-responsive platelets are often found in essential hypertension. It has also been suggested that in hypertensive patients platelets may serve as an easily accessible indicator of abnormalities in contractile cell function. To test these suggestions, we analysed the relationship between platelet aggregation and genetic hypertension in the rat. METHODS: Linear regression analysis of mean values of recombinant inbred strains was used to evaluate the relationship between blood pressure and ADP-induced platelet aggregation. RESULTS: ADP-induced platelet aggregation in platelet-rich plasma in spontaneously hypertensive rats (SHR) was significantly decreased compared with in normotensive Brown Norway (BN) rats. However, in recombinant inbred strains, derived from (SHR x BN) F2 hybrids, correlation analysis revealed that platelet aggregation and blood pressure are independent traits. CONCLUSIONS: The present results suggest strongly that spontaneous hypertension and platelet hypo-aggregability in SHR were linked together by chance due to drift during selective inbreeding. The absence of a correlation between the two traits also indicates that alterations in platelet function in essential hypertension, often found in population-based studies, may have to be reaffirmed in genetically better-defined situations, e.g. by pedigree analysis.

Animals↗
PubMed1985

[Inhibition of platelet aggregation and thromboxane formation by the calcium antagonist nisoldipine following a single oral dose of 10 mg. A double-blind study in healthy probands].

The influence of the calcium antagonist nisoldipine on collagen-induced platelet aggregation and platelet thromboxane formation was studied ex vivo in healthy male volunteers in a double-blind, placebo-controlled crossover design. Measurements of general haemodynamics, immunoreactive 6-oxo-prostaglandin F1 alpha and thromboxane B2 ex vivo and collagen-induced (0.6 and 2.5 micrograms/ml) platelet aggregation were performed immediately before (time 0), 0.5 h, 1 h and 2 h after ingestion of 10 mg nisoldipine or an identical placebo tablet. Compared with the control response at time 0, administration of nisoldipine resulted in a significant inhibition of both low-collagen-induced platelet aggregation and formation of immunoreactive thromboxane B2 at time 0.5 h. There were no changes in heart rate or systolic blood pressure but a significant decrease in diastolic blood pressure by nisoldipine at 1 h. No such change was obtained with placebo and there were also no alterations with nisoldipine in platelet aggregation and thromboxane formation after stimulation by high-dose collagen at this or any other time of the study. The data demonstrate a platelet-inhibitory potential of nisoldipine in healthy men which is probably related to an increased resistance of the platelet membrane against foreign stimuli.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

The effect of chloramphenicol and cycloheximide on platelet aggregation and protein synthesis.

This study investigated the role of platelet protein synthesis in platelet aggregation. Cycloheximide (Cx) and chloramphenicol (Cm) were used as inhibitors of cytoplasmic (80S ribosome directed) and mitochondrial protein synthesis respectively. The effect of these agents on human platelet aggregation and L-[U-14C]leucine incorporation into platelet protein was investigated. Cm exhibited dose-dependent inhibition of collagen, thrombin and secondary ADP aggregatory responses, but had no effect on arachidonate or primary ADP responses over a similar concentration range (3.1 X 10(-3), 3.1 X 10(-4) and 3.1 X 10(-5) M). Cm also inhibited platelet secretion associated with collagen and secondary ADP responses. Furthermore, Cm exhibited a similar dose-dependent inhibition of L-[U-14C]leucine incorporation into platelet protein reaching 80% inhibition of incorporation at 3 X 10(-3) M. At similar concentrations (3.5 X 10(-3), 3.5 X 10(-4) and 3.5 X 10(-5) M) Cx failed to show inhibition of human platelet aggregation by all agonists used with the exception of collagen where some inhibition was seen at high Cx concentration (3.5 X 10(-3) M). Cx was also found to be ineffective at inhibiting L-[U-14C]leucine incorporation into platelet protein at all concentrations tested. These results suggest that the majority of platelet protein synthesis is mitochondrial and that this protein synthesis may have a role in human platelet aggregation.

Blood Platelets↗
PubMed1995

The mechanism of cold-induced platelet aggregation in the presence of heparin.

Low temperature induces platelet aggregation, but this phenomenon is slight and poorly reproduced. However, heparin potentiated the reaction in a dose dependent manner. The degree of aggregation increased as the temperature at which the platelet-rich plasma was chilled was lowered, and as the time of chilling lengthened. Acetylsalicylic acid, a cyclooxygenase inhibitor, and staurosporin, an inhibitor of protein kinase C, partially inhibited cold-induced platelet aggregation (CIPA), suggesting that at least part of the reaction mechanism involves production of thromboxane A2 and activation of protein kinase C. Prostaglandin E1 (PGE1), which inhibits platelet responses through elevating platelet cyclic AMP, completely blocked CIPA, suggesting that PGE1 dependent pathway in platelets plays an important role for CIPA. The inhibition of CIPA by these inhibitors suggests that CIPA is aggregation with platelet activation but not platelet agglutination. Extracellular Ca2+ is essential for CIPA because ethylene glycol-bis (beta-aminoethylether) N, N, N', N'-tetraacetic acid (EGTA), extracellular Ca2+ chelating agent, completely inhibited CIPA. Monoclonal antibodies against glycoprotein (GP) IIb/IIIa (10E5, P2) and Ang-Gly-Asp-Ser-peptide (RGDS-peptide) which inhibit fibrinogen binding to GPIIb/IIIa completely blocked CIPA but monoclonal antibodies against GPIb (6D1, SZ2) partially. In addition, CIPA occurred only when fibrinogen was added to washed platelets suspension. These results indicate that CIPA is dependent on binding of fibrinogen to GPIIb/IIIa and GPIb is partly related with the reaction.

Amino Acid Sequence↗
PubMed1984

Primary hypercholesterolemia: effect of treatment on serum lipids, lipoprotein fractions, cholesterol absorption, sterol balance, and platelet aggregation.

The nonabsorbable bile acid sequestrant resin, colestipol, was administered to 16 patients with primary hypercholesterolemia, and its effect on serum lipids, lipoprotein fractions, and circulating platelet aggregate ratio and platelet aggregation in response to adenosine diphosphate (ADP) was compared with that of sitosterol. Cholesterol absorption and sterol balance studies were done in four of the subjects during the following treatment periods: diet alone, colestipol, and sitosterol. Total serum cholesterol was significantly reduced by colestipol but only slightly decreased by sitosterol. Combination treatment with colestipol and sitosterol was associated with a smaller decrease in serum cholesterol than was demonstrated with colestipol alone. Serum triglycerides tended to increase during colestipol therapy (this increase was not clinically significant) but showed a minimal nonsignificant decrease with sitosterol treatment. Colestipol decreased cholesterol absorption, whereas sitosterol slightly increased it. Fecal sterol excretion was increased with colestipol treatment but was minimally affected by administration of sitosterol. Low-density lipoprotein and high-density lipoprotein cholesterol significantly decreased with colestipol treatment. The circulating platelet aggregate ratio was significantly lower in the group of patients with hypercholesterolemia who received colestipol initially than in control subjects, but platelet aggregation in response to ADP was not significantly different between these two groups. No significant change in platelet aggregation was noted during colestipol or sitosterol treatment despite a significant decrease in total serum cholesterol with colestipol therapy, a suggestion that the platelet and lipid abnormalities are not interrelated.

Adenosine Diphosphate↗
PubMed1986

Hemostatic mechanisms, independent of platelet aggregation, arrest gastric mucosal bleeding.

Platelet adhesion, aggregation, and subsequent plug formation play a major role in the control of cutaneous and vascular hemostasis. Little is known, however, about the hemostatic processes in gastric mucosal tissue. A method for evaluating bleeding from a standard incision in the gastric mucosa of the rat, rabbit, and dog has therefore been developed. By using pharmacological agents that interfere with platelet aggregation and blood coagulation, the mechanism of gastric hemostasis has been compared to that in the vasculature, using the rat mesenteric artery. Intravenous infusion of prostacyclin (0.5 micrograms X kg-1 X min-1), which inhibits platelet aggregation directly, or administration of the thromboxane synthase inhibitor 1-benzylimidazole (50 mg X kg-1) significantly prolonged bleeding in the mesenteric artery yet failed to alter gastric mucosal bleeding. In contrast, a low dose of heparin (100 units X kg-1), which interferes with the clotting process, had no effect on mesenteric bleeding but substantially prolonged bleeding from the gastric mucosa. These findings suggest that, unlike in the skin or vasculature, platelet aggregation plays a minimal role in the initial hemostatic events in the gastric mucosa and that the arrest of gastric hemorrhage is brought about largely by processes primarily involving the coagulation system.

Animals↗
PubMed1995

Effect of non-saponin fraction from Panax ginseng on cGMP and thromboxane A2 in human platelet aggregation.

The non-saponin fraction (NSF; lipophilic fraction) from the roots of Panax ginseng inhibited the aggregation of human platelets induced by thrombin (0.1 units/ml) in a dose-dependent manner. NSF induced the elevation of cGMP concentration in human platelets in a similar manner to molsidomine, a known vasodilator. NSF also inhibited Ca(2+)-influx into platelets. While verapamil, a Ca(2+)-antagonist, increased the cAMP level in platelets stimulated by thrombin, NSF had little effect on cAMP formation. Instead, NSF potently inhibited the thromboxane A2 (TXA2) production. The results suggest that NSF may regulate the levels of cGMP and TXA2 to inhibit platelet aggregation induced by thrombin.

Alkynes↗
PubMed1992

Assessment of whole-blood spontaneous platelet aggregation during pregnancy using an impedance particle counter.

The slide test method of Velaskar and Chitre for determining platelet aggregation in whole blood after induction of aggregation was modified for spontaneous platelet aggregation and evaluated. The reproducibility was satisfactory (CV 1-3%). The results obtained with this method and the method of Velaskar were not significantly different. The Spearman rank correlation was 0.75 (p less than 0.0001). We established reference values for the particle counter method and Velaskar's method in pregnant and non-pregnant women; no significant change in spontaneous platelet aggregation was seen throughout pregnancy. In order to estimate the clinical value of the test in pregnancy, we followed up a number of pregnant patients with primary enhanced spontaneous whole-blood platelet aggregation before and after treatment with low-dose acetylsalicylic acid. The test was found to be suited for the detection of spontaneous whole-blood platelet aggregation and for the follow-up after treatment with acetylsalicylic acid. Further studies are necessary, however, to assess the predictive value of an aberrant test result during pregnancy.

Adolescent↗
PubMed1997

Platelet aggregation is impaired during anaesthesia with sevoflurane but not with isoflurane.

PURPOSE: Halothane suppresses platelet aggregation in vitro and ex vivo, and prolongs bleeding time. In a previous in vitro study we demonstrated that sevoflurane had a more suppressive effect on platelet aggregation than did halothane. The present study investigated whether the clinical use of sevoflurane affected platelet aggregation ex vivo. METHODS: Thirty-eight patients undergoing minor elective surgery were divided randomly into sevoflurane and isoflurane groups. Anaesthesia was induced with thiopentone i.v., and was maintained with sevoflurane or isoflurane with nitrous oxide. Blood was collected to measure platelet aggregation induced by adenosine diphosphate (ADP) and epinephrine. The first (control) blood collection was performed in the operating room before induction of anaesthesia, and the second 5-10 min after tracheal intubation but before the start of surgery, when the end-expiratory sevoflurane or isoflurane concentrations had stabilised at 1-1.5 times the minimum alveolar concentration (MAC) and mean arterial pressures were between 80-120% of preanaesthetic values. RESULTS: In all samples obtained during sevoflurane anaesthesia (n = 15), ADP and epinephrine could not induce secondary aggregation, although they did induce primary aggregation. In contrast, in the isoflurane group, both primary and secondary aggregation were observed in 14 out of 15 patients, and secondary aggregation was abolished in only one of the samples obtained during anaesthesia. CONCLUSIONS: Sevoflurane, but not isoflurane, alters platelet aggregation in the clinical situation, possibly by suppression of thromboxane A2 formation.

Adult↗
PubMed1993

Circulating platelet aggregates indicative of in vivo platelet activation in pulmonary hypertension.

The authors investigated the existence of circulating cellular aggregates in 12 patients with moderate to severe pulmonary hypertension, using scanning electron microscopy. Peripheral venous blood was collected in the presence of 11.5 mM buffered ethylenediaminetetraacetic acid, in order to disperse freshly formed disaggregable aggregates. Irreversible aggregates represented by platelet clusters and/or platelet attachment to either leukocytes or red cells were identified in 7 patients with pulmonary hypertension. Endogenous platelet activation was further confirmed by a significant increase in plasma levels of beta-thromboglobulin in comparison with controls (33.8 +/- 14.1 vs 22.7 +/- 11.5 ng/mL respectively, p < 0.025). The presence of irreversible aggregates in the blood stream strongly suggests that cell-cell interactions actually occur in vivo in these patients. If so, therapeutic measures aimed at preventing in situ thrombosis and its consequences may be beneficial in this disorder.

Adolescent↗
PubMedDate not supplied

[Kinetic analysis of induced platelet aggregation].

Two mathematic models depicting the kinetics of induced platelet aggregation are suggested. The mechanisms of platelet aggregation involving the reactions of the inductor molecules with membrane receptors and intercellular interactions of platelets are discussed. Analytical expressions depicting the changes in the amount of platelets in the aggregation population and in the course of aggregation are offered. A procedure for calculating the kinetic parameters according to the experimental data is presented. The parameters of aggregation induced by different substances are calculated with the use of computers. It has been shown that application of mathematic stimulation provides valuable information both during the study of the mechanisms and for quantitative analysis of platelet aggregation.

Adenosine Diphosphate↗
PubMed1990

Potentiation of anti-platelet aggregating activity of cilostazol with vascular endothelial cells.

We developed the new system in which the platelet aggregation was detected turbidimetrically using glass cuvettes which were coated cultured vascular endothelial cells. Using this system, we evaluated the effect of cilostazol, having a selective inhibitory effect on cAMP-PDE, on the ADP-induced platelet aggregation in the presence of endothelial cells. Cilostazol inhibited the platelet aggregation dose-dependently in the presence or absence of endothelial cells. The inhibitory effect of cilostazol on platelet aggregation was potentiated by the presence of endothelial cells, and the slope of the dose-response curves were identified to be as the same between both experiments in the presence and the absence of endothelial cells. The pretreatment of endothelial cells with aspirin reversed the potentiated inhibitory effect of cilostazol on the platelet aggregation with endothelial cells. The amount of 6-keto-prostaglandin F1 alpha accumulated in the cuvette was reduced in this condition. On the other hand, the inhibitory effect of prostaglandin E1 on the platelet aggregation was not potentiated by the presence of endothelial cells. These results suggest that the endothelium-derived prostacyclin plays a role on the potentiation of anti-platelet aggregatory effect of cilostazol.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

1-O-hexadecyl-2-metoxy-glycero-3-phosphatidylcholine--a methoxy ether lipid inhibiting platelet activating factor-induced platelet aggregation and neutrophil oxidative metabolism.

Whether or not two alkylglycerols could initiate a functional response in human platelets or modify responses induced by platelet activating factor (PAF) was evaluated. It was found that 1-100 microM 1-O-hexadecyl-2-metoxy-glycero-3-phosphatidylcholine (Et-16-OCH3) induced platelet aggregation but 1-O-hexadecyl-sn-glycerol (chimyl alcohol; CA) did not. Et-16-OCH3-induced platelet aggregation was abolished by pretreatment with the PAF receptor antagonist WEB 2086. While CA had no effect on platelet aggregation induced by PAF, pretreatment with Et-16-OCH3 (0.1 microM or higher) significantly inhibited platelet aggregation induced by PAF, but had no effect on aggregation caused by ADP, thrombin or phorbol myristate acetate (PMA). A receptor binding study using radiolabelled [3H]WEB 2086 showed that Et-16-OCH3 exerts its actions through interaction with the PAF receptor. Moreover, Et-16-OCH3 inhibited neutrophil chemiluminescence responses induced by PAF, but not reactions to PMA or a formyl peptide. Finally, 1 microM Et-16-OCH3 induced a rise in the intracellular calcium concentration in platelets equal to that induced by PAF and also had an calcium ionophore-like effect at 100 microM. Thus, this study shows that Et-16-OCH3 is both a potent inducer of platelet aggregation and an inhibitor of PAF-induced platelet aggregation and neutrophil chemiluminescence, through interaction with the PAF receptor.

Azepines↗
PubMed2005

Inhibitory mechanisms of low concentrations of oxidized low-density lipoprotein on platelet aggregation.

The intracellular mechanisms underlying oxidized low-density lipoprotein (oxLDL)-signaling pathways in platelets are not yet completely understood. Therefore, the aim of this study was to further examine the effects of oxLDL in prevention of platelet aggregation. In this study, oxLDL concentration-dependently (40-120 microg/ml) inhibited platelet aggregation in human platelet-rich plasma stimulated by agonists. Moreover, oxLDL (40 and 80 microg/ml) markedly decreased the fluorescence intensity of platelet membranes tagged with diphenylhexatriene. Rapid phosphorylation of a protein of Mr 47,000 (P47), a marker of protein kinase C activation, was triggered by PDBu (150 nM). This phosphorylation was markedly inhibited by oxLDL (40 and 80 microg/ml) in phosphorus-32-labeled platelets. In addition, oxLDL (40 and 80 microg/ml) markedly increased levels of cyclic AMP and cyclic AMP-induced vasodilator-stimulated phosphoprotein (VASP) Ser(157) phosphorylation. The thrombin-evoked increase in pHi was inhibited in the presence of oxLDL (40 and 80 microg/ml). These results indicate that the antiplatelet activity of oxLDL may involve the following pathways. (1) oxLDL may initially induce conformational changes in platelet membranes, leading to inhibition of the activation of protein kinase C, followed by inhibition of P47 protein phosphorylation, and intracellular Ca(2+) mobilization. (2) oxLDL also activated formation of cyclic AMP and cyclic AMP-induced VASP Ser(157) phosphorylation, resulting in inhibition of the Na(+)/H(+)exchanger; this leads to reduced intracellular Ca(2+) mobilization, and ultimately to inhibition of platelet aggregation. This study further provides new insights concerning the effects of low concentrations of oxLDL on platelet aggregation.

Calcium↗
PubMed1987

Inhibition of thrombin-induced platelet aggregation by high molecular weight kininogen.

1. Thrombin-induced platelet aggregation and cleavage of [3H]FSBA-labeled aggregin is mediated by platelet calpain. 2. Plasma HMWK inhibits platelet aggregation and cleavage of aggregin in intact platelets, indirectly by thrombin and directly by calpain. 3. Inhibition of thrombin-induced platelet aggregation by HMWK is specific for this proteolytic enzyme. 4. HMWK is the major inhibitor of thrombin-induced activation of platelets in plasma.

Fibrinogen↗
PubMedDate not supplied

Effects of mitoxantrone and bisantrene on platelet aggregation and prostaglandin/thromboxane biosynthesis in vitro.

The effects of mitoxantrone and bisantrene on agonist-stimulated platelet aggregation, prostaglandin E2 and thromboxane B2 production were examined and results compared with those produced by indomethacin and acetylsalicylic acid. Both mitoxantrone and bisantrene effectively inhibited collagen-, ADP-, and epinephrine-stimulated platelet aggregation. Collagen (0.54 microgram/ml)-stimulated platelet aggregation was inhibited by 50% at 60 microM mitoxantrone and 8 microM bisantrene. The concentration of drug required for inhibition of platelet aggregation varied inversely with the level of collagen stimulus employed. Mitoxantrone and bisantrene inhibited both the first and second phase of epinephrine-stimulated platelet aggregation. Complete inhibition of the second wave of aggregation was obtained at greater than 160 microM mitoxantrone and 16 microM bisantrene. Mitoxantrone is comparable in potency to acetylsalicylic acid which inhibited the second wave of epinephrine-stimulated aggregation 50% at 160 microM, whereas bisantrene may be compared to indomethacin which produced complete inhibition of aggregation at 16 microM. Production of PGE2 and TXB2 in epinephrine-stimulated platelets was inhibited by both drugs with 50% inhibition of PGE2 production occurring at 12 microM mitoxantrone and 3 microM bisantrene. Thromboxane B2 production was inhibited by 50% at 10 microM mitoxantrone and 5 microM bisantrene. Indomethacin inhibited PGE2 and TXB2 production 50% at 4 microM. Thus mitoxantrone and bisantrene inhibit platelet aggregation and prostaglandin production which may be of significance in metastasis and in prostaglandin-mediated physiologic and immune responses.

Adult↗
PubMedDate not supplied

[Effect of dietary linoleic acid on the platelet aggregation, fatty acid composition of platelet phospholipids and synthesis of platelet prostaglandins in rats].

Three groups of Wistar-Kyoto rats were kept on diets containing different quantity of linoleic acid (LA) in prenatal and postnatal periods up to 18 weeks age: I. less than 0.1 cal.% of LA, 2. 9.0 cal.% of LA and 3. 16 cal.% of LA. Aggregation of washed platelets with ADP and A23187, biosynthesis of prostaglandins from 14C-arachidonic acid in platelets and fatty acid composition of platelet phospholipids were studied using gas liquid chromatography. Modification of fatty acid composition of platelet phospholipids and changes in biosynthesis of platelet prostaglandins are the base for proaggregation effect of LA deficient and for antiaggregation effect of LA enriched diets. The effects of dietary LA were mediated not only via altered metabolism of fatty acids of linoleic family but also via metabolism of fatty acids of oleic and linolenic series.

Animals↗
PubMed1984

Effect of a single Ditazole dose on platelet aggregation and prostaglandin formation.

The in vitro activity of the non-steroidal anti-inflammatory agent Ditazole was investigated in a group of 20 male patients at thrombotic risk in comparison with placebo in a completely randomized cross-over design. A single Ditazole administration was able to induce a significant decrease in the number of circulating platelet aggregates (CPA), platelet aggregability by ADP and in thromboxane production by platelets. No significant changes were found in platelet cAMP concentration and in plasma 6keto-PGF1 alpha levels. Present results indicate that Ditazole affects platelet aggregation in a double way, by decreasing both the reversible and the ADP-induced aggregation. The lack of effects on plasma 6keto-PGF1 alpha concentration suggests that Ditazole can reduce platelet aggregation without affecting prostacyclin production.

6-Ketoprostaglandin F1 alpha↗