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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The goals of this study were 1) to quantitate the effects of atherosclerosis on physiological and pharmacological endothelium-dependent vasoactive responses in coronary arterioles downstream from arterial lesions and 2) to determine if administration of L-arginine, the precursor for endothelium-derived was induced in pigs, and vasomotor responses of isolated, cannulated coronary arterioles (30-70 microns in diameter) were assessed by measuring diameter changes in vitro. To assess pharmacological alterations of endothelium-dependent responses, dose-response curves were constructed to ADP, serotonin, and histamine. To assess physiological alterations in endothelial function, different flow rates were established across the vessel. Arteriolar diameters were measured in vessels from normal and atherosclerotic pigs under control conditions, after administration of L-arginine, and after endothelial denudation. In arterioles from normal pigs, administration of serotonin, histamine, or ADP produced dose-dependent vasodilation, which was abolished by endothelial denudation. In arterioles from atherosclerotic pigs, administration of histamine, serotonin, and ADP produced dilation at only the highest doses (10(-6)-10(-7) M), and the extent of dilation was only 20-30% of that observed in arterioles from normal pigs. Initiation of flow also produced vasodilation in arterioles from normal pigs that was completely abolished after endothelial denudation. In arterioles from atherosclerotic pigs, flow-induced responses were absent. These abnormal physiological and pharmacological responses (i.e., blunted vasodilation to pharmacological stimulation and to flow) were restored after administration of L-arginine for 40 minutes. The vascular responses after administration of L-arginine were not different from those observed under control conditions in arterioles from normal pigs. In addition, L-arginine did not restore vasodilation to the endothelium-dependent agonists in denuded segments. From these data in arterioles downstream from atherosclerotic lesions, we conclude that 1) the ED50 and maximal responses of endothelium-dependent vasodilation to ADP, histamine, and serotonin are attenuated; 2) the physiological response to flow, that is, flow-mediated endothelium-dependent vasodilation, is absent; and 3) the abnormality in arteriolar responsiveness during large vessel disease involves an impairment of the synthesis and/or release of endothelium-derived relaxing factor.
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PMID:Pathophysiological consequences of atherosclerosis extend into the coronary microcirculation. Restoration of endothelium-dependent responses by L-arginine. 153 85

The effects of prolonged in vivo heparin treatment upon vasomotor responses and content of cholesterol and energy related compounds were studied in isolated thoracic and abdominal aortas from Watanabe heritable hyperlipidemic (WHHL) rabbits. Unfractionated heparin was administered subcutaneously (2 mg/kg twice a day) to 3-month-old WHHL rabbits for a period of 6 months. A group of WHHL rabbits was treated with saline solution and considered as control. Aortic cholesterol infiltration and serum cholesterol were not significantly decreased by the prolonged heparin treatment. In heparin-treated WHHL rabbits, the in vitro aortic endothelium-dependent relaxation produced by acetylcholine or calcimycin (A 23187) was greater than in saline-treated WHHL group. ATP-induced aorta relaxation (endothelium-dependent and endothelium-independent) did not vary significantly in the two groups of WHHL rabbits, even after mechanical removal of endothelium. Also the noradrenaline-induced aorta contraction did not vary between the two groups of WHHL rabbits. No significant variation in energy-related compounds (except for ADP) was found in the aortic arch. These results suggest that heparin produces a protective effect on aortic tissue by acting mainly at endothelial level.
Atherosclerosis 1992 Jan
PMID:Protective role of heparin on in vitro functional aortic response in Watanabe heritable hyperlipidemic rabbits. 157 18

The effects of aspirin, nifedipine, dipyridamole and cavinton on platelet aggregability in patients with atherosclerosis has been studied using various agents to induce aggregation. The drugs reduced platelet aggregability when aggregation was induced by ADP, adrenaline, or collagen alone. However, if platelet aggregation were induced by combinations of the agonists (including combinations of ADP with either adrenaline or platelet-activating factor (PAF), adrenaline with PAF, and collagen with ADP), the anti-aggregant effects of aspirin, dipyridamole, and cavinton were significantly reduced. The effect of nifedipine was less markedly reduced, especially by combinations which included adrenaline. The data suggest that positive agonist interactions may lead to a reduction in the therapeutic activity of antiplatelet drugs.
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PMID:Effects of aspirin, dipyridamole, nifedipine and cavinton which act on platelet aggregation induced by different aggregating agents alone and in combination. 157 42

Dialysis patients have an inordinate risk of cardiovascular events. Fish oils, rich in n-3 fatty acids, are believed to be beneficial in the prevention of atherosclerosis and thrombosis. Hence, the use of fish oils deserves consideration as a preventative or therapeutic intervention in dialysis patients. The suggestion has been made that n-3 fatty acids could increase the risk of bleeding, and thus, the safety of the use of these agents in dialysis patients must be established before long-term studies are undertaken. This study addresses the effect of n-3 fatty acids on the hemostatic profile of dialysis patients. Sixteen patients on chronic dialysis therapy were randomized to fish oil (MaxEPA) or placebo (olive oil) in a double-blind cross-over study. They received 3.6 g of n-3 fatty acids for 4 wk. Bleeding times were 4.8 +/- 0.4 min on MaxEPA and 4.5 +/- 0.3 min on placebo. Platelet aggregation to low-dose ADP or collagen also remained unchanged. There was a trend to lower serum triglyceride levels (2.7 +/- 0.5 versus 3.4 +/- 0.6 mmol/L, fish oil versus placebo) that did not reach statistical significance. Gastrointestinal side effects occurred in 10 of the 16 subjects and were severe in 5 patients. These side effects occurred in both the olive oil and the fish oil groups. The study had a 95% chance of detecting a clinically doubling significant increase in bleeding time, i.e., beta error less than 5%. In conclusion, n-3 fatty acids do not introduce a clinically important risk of bleeding for patients with end-stage renal disease.
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PMID:Effect of n-3 fatty acids from fish oil on hemostasis, blood pressure, and lipid profile of dialysis patients. 161 Sep 84

In a double blind, randomized trial, the effects of aspirin (1, 5, and 15 mg/kg) were compared with the changes in platelet aggregation at 6 and 24 hours after dosage. It is found that there is a negative correlation between aspirin hydrolysis velocity in blood and capability of aspirin to decrease platelet aggregation with ADP and collagen in patients with atherosclerosis. Relationship between these parameters depends on aspirin dosage. The correlation was more marked for low doses of aspirin. It is suggested that the effect of aspirin in low dosage on platelet aggregation might be ineffective in many patients without control of aspirin hydrolysis velocity in blood.
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PMID:Dose-dependent aspirin hydrolysis and platelet aggregation in patients with atherosclerosis. 161 22

Clopidogrel is a new thieno-pyridine derivative and has a more potent inhibitory effect on platelet aggregation, dependent on ADP rather than ticlopidine. In a phase I study performed in Japan, significant inhibition of ADP-induced platelet aggregation and prolongation of bleeding time was observed in the dose range of 25, 50 and 75 mg. These effects were comparable to 200 or 300 mg of ticlopidine. Antithrombotic effects have also been shown in experimental animal models. Clopidogrel is expected to reduce the incidence of neutropenia since smaller doses are sufficient to suppress platelet aggregation compared to ticlopidine. Clopidogrel has been proven to be a potent and well-tolerated antiplatelet agent for atherosclerosis patients at risk of thrombosis, in Europe.
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PMID:[Antiplatelet effect of clopidogrel]. 161 93

The influence of a 4-weeks therapy with 500 mg ticlopidine daily on platelet function parameters was examined in 10 male healthy volunteers aged 20-33 years in order to extend the knowledge on the antiplatelet activity of this substance. Ticlopidine significantly (p less than 0.01) affected ex-vivo platelet aggregation induced by ADP and increased platelet sensitivity to the antiaggregatory action of PGI2. Generation of TXB2 from endogenous substrate during spontaneous clotting of blood (serum-TXB2), conversion of exogenous radiolabelled arachidonic acid into TXB2 and MDA-formation in isolated platelets were unaffected by the treatment. The TXB2-level in plasma of volunteers, however, was decreased, after administration of the drug. The diminished alpha-granule content liberation (beta-thromboglobulin: p less than 0.01; PDGF: p less than 0.01; PF4 not significant) indicates that ticlopidine induces a decrease in platelet activity. The beneficial effect on release reaction is not associated with a decrease in TXA2-formation. Our results demonstrate that ticlopidine inhibits platelet activity, especially the PDGF-release. These results confirm the value of this drug in the prevention of atherosclerosis and its thromboembolic complications.
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PMID:Ticlopidine and platelet function in healthy volunteers. 161 96

The aim of this study was to determine the significance of the "coronary factor" in patients with essential hypertension (EH). Electrocardiogram Holter monitoring was performed in 61 patients with EH stage II (according to the World Health Organization criteria). Silent, ie, painless ST-segment depression, was found in 34 patients on whom echocardiography, a treadmill test, and transesophageal pacing were performed. In 21 patients with EH and silent ischemia, the examination included 201Tl stress scintigraphy, coronary angiography, and a platelet aggregation test. In 15 patients, catecholamines and beta-endorphins were obtained in blood samples during silent ischemia. 201Tl scintigraphy showed transient defects of perfusion without clearance abnormalities (group I) and with clearance abnormalities (group II). The patients in group I had more severe left ventricular hypertrophy (LVH) and a significantly higher platelet aggregation response to 0.5 mumol/L adenosine diphosphate; one patient in this group had coronary atherosclerosis. LVH and the platelet aggregation response was less pronounced in the patients in group II, but atherosclerotic lesions of a coronary artery were observed in four patients. In both groups, norepinephrine and beta-endorphin levels were increased during silent episodes of ischemia. The results suggest that there are different pathogenetic mechanisms of coronary insufficiency in patients with EH, a hypertensive heart, and silent ischemia.
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PMID:Silent myocardial ischemia in patients with essential hypertension. 163 37

Twenty patients with obliterative atherosclerosis in the lower extremities arteries (Fontaine's stage II) were treated with nitrendipine (Bayotensin) given in the dose of 20 mg daily for 6 weeks. This therapy with nitrendipine produced improvement manifested by the prolongation of the distance of intermittent claudication, shortening of pain duration, increase in blood flow in the ischemic extremity, and increase in pressure index. At the same time, nitrendipine decreased ADP-produced platelet aggregation and activated fibrinolytic system. Clinical trials have shown that nitrendipine is effective in the obliterative atherosclerosis in the lower extremities.
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PMID:[Use of nitrendipine in treating patients with obliterative atherosclerosis of arteries in the lower extremities]. 166 21

The endothelial cells can release both relaxing and contracting substances. The former include prostacyclin and endothelium-derived relaxing factor (EDRF, which most likely is nitric oxide, or a nitrosoderivative releasing nitric oxide, derived from L-arginine). Candidates as endothelium-derived contracting factors (EDCF) include superoxide anions thromboxane A2 and the peptide endothelin. Endothelium-derived relaxing factor causes relaxation of vascular smooth muscle by activation of the soluble form of guanylate cyclase which leads to an accumulation of cyclic GMP; it also reduces platelet adhesion and aggregation. The latter effect is synergistic with the inhibition evoked by prostacyclin. The release of EDRF and prostacyclin plays a key role in the protective role of the endothelium against vasospasm and the unwanted coagulation of blood. Indeed, thrombin and aggregating platelets are potent stimuli for the release of EDRF. The platelet-products responsible are the adenine nucleotides, ADP and ATP, which activate P2y-purinergic receptors on the endothelial cells and 5-hydroxytryptamine (serotonin) that stimulates 5-HT1-like serotonergic receptors. The response to serotonin, but not that to the adenine nucleotides, is mediated by a pertussis toxin-sensitive mechanism. When endothelial cells regenerate, or are cultured, they selectively lose the pertussis toxin-sensitive mechanism of release, which results in a marked decrease in sensitivity to exogenous and platelet-released serotonin. As a consequence, the endothelial cells exhibit a considerably reduced response to aggregating platelets. This phenomenon, which can be exacerbated by hypercholesterolemia, favors ongoing platelet aggregation and vasospasm, and constitutes a first step toward atherosclerosis.
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PMID:Platelet-derived serotonin, the endothelium, and cardiovascular disease. 171 75


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