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

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

The effects of prostacyclin and its stable analogues on endothelin-induced DNA synthesis were investigated in cultured vascular smooth muscle cells. Aortic smooth muscle cells were obtained from male Wistar rats. In order to eliminate endothelial cells, the cells were cloned. DNA synthesis in intact cells was estimated by [3H]thymidine incorporation. Prostacyclin and its stable analogues (TEI-7165, TEI-9090, TEI-1324, TEI-3356, and TEI-9063) inhibited the endothelin-induced DNA synthesis with an IC50 of 1-30 nM. These results indicate that prostacyclin and its stable analogues are possibly effective in preventing the proliferation of vascular smooth muscle cells under some pathological situations, including atherosclerosis.
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PMID:Inhibition of endothelin-1-induced DNA synthesis by prostacyclin and its stable analogues in vascular smooth muscle cells. 172 24

The endothelium not only mediates relaxation but is a source of contracting factors. Endothelium-dependent contractions are elicited by physical and chemical stimuli (i.e., hypoxia, pressure, and stretch) and autacoids, local and circulating hormones. The mechanism of endothelium-dependent contractions to hypoxia involves withdrawal of nitric oxide. The endothelial cyclooxygenase pathway can produce thromboxane A2, prostaglandin H2, and superoxide anions. The peptide endothelin is a potent contracting factor; its production is stimulated by vasopressor hormones, platelet-derived factors, coagulation products, and cytokines, whereas endothelium-derived nitric oxide, prostacyclin, and a smooth muscle cell-derived inhibitory factor reduce endothelin production. In hypertension, the release of cyclooxygenase-dependent endothelium-derived contracting factors to stretch, acetylcholine, and platelet-derived products is augmented. Vascular endothelin production in hypertension remains controversial but appears mostly normal; it is augmented in the presence of vascular disease or renal insufficiency. The endothelium-dependent inhibition of endothelin-induced contractions is reduced in hypertension while the reactivity of vascular smooth muscle may be normal, increased, or reduced. The potentiating effects of low concentrations of endothelin on contractions to norepinephrine are augmented with aging and hypertension. In atherosclerosis, the production of the cyclooxygenase-dependent endothelium-derived contracting factors and endothelin is enhanced. Thus, endothelium-derived contracting factors can profoundly affect vascular tone and counteract relaxing factors produced within the endothelium. In hypertension and atherosclerosis, the role of contracting factors appears to become more dominant, leading to an imbalance of endothelium-dependent vascular regulation.
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PMID:Endothelium-derived contracting factors. 173 45

Basal release of endothelium-derived relaxing factor (EDRF) and prostacyclin from intact vascular endothelium may inhibit continuously platelet aggregation. If local platelet aggregation occurs, platelet-derived adenine nucleotides stimulate the release of EDRF. Stimulated EDRF release may override the direct vasoconstrictor effects of other platelet products such as thromboxane and serotonin resulting in local vasodilatation. In addition, stimulation of EDRF release by adenine nucleotides may inhibit further platelet adhesion and aggregation by a feedback mechanism. Thus, intact vascular endothelium may play an important role in the defense against platelet deposition and vasospasm. In atherosclerosis, basal and stimulated release of EDRF is markedly reduced. Endothelial dysfunction will impair this protective mechanism and will favour vasoconstriction and further platelet disposition. Occurrence of occlusive thrombus formation in patients with coronary artery disease may be pathophysiologically related to this impairment of endothelial defense.
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PMID:Platelets, endothelium-dependent responses and atherosclerosis. 175 24

The interaction of platelets with the vessel wall plays an important pathophysiological role in coronary artery disease. While in healthy blood vessels platelets remain inactivated and do not adhere or aggregate, an augmented interaction occurs in coronary artery disease. Due to their strategic anatomical position between the circulating blood and the media of the vascular wall, endothelial cells play an important regulatory role. Indeed, after endothelial denudation, massive platelet adhesion and aggregation at the vessel wall occurs. Platelet-derived substances lead to vasoconstriction and in the long run also to proliferative changes of the vascular wall. Besides other substances, endothelial cells release vasoactive mediators such as endothelium-derived nitric oxide (NO), prostacyclin and endothelin. In healthy human arteries, aggregating platelets cause endothelium-dependent relaxations in spite of the liberation of serotonin and thromboxane A2 and through the luminally released NO also induce a feedback inhibition of the platelets. In contrast, in arteries without endothelium, a marked vasoconstriction (due to thromboxane A2 and serotonin) is noted. Endothelin may also play a role in platelet-vessel wall interaction, since thrombin and transforming growth factor beta (a platelet-derived product) stimulate the production of this potent vasoconstrictor. Oxidized low-density lipoproteins inhibit the relase of NO and thereby activate the platelet-vessel wall interaction. In atherosclerosis even more pronounced dysfunctions of the endothelium occur, which lead to vasoconstriction, ischemia and thrombus formation in patients with coronary artery disease.
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PMID:[Thrombocyte-vascular wall interaction and coronary heart disease]. 176

Baroreceptors located in carotid sinuses and aortic arch are activated with increases in arterial pressure. The increased afferent nerve activity triggers reflex adjustments that buffer the rise in pressure. Mechanical deformation of baroreceptor nerve endings is considered the primary mechanism of receptor activation. Recent studies in our laboratory have demonstrated that prostanoids, most likely released from endothelial cells during stretch, contribute--as paracrine factors--to the activation of baroreceptors. Exposure of the isolated carotid sinus in anesthetized rabbits to prostacyclin (PGI2) or arachidonic acid increases baroreceptor sensitivity whereas inhibition of endogenous formation of prostanoids with indomethacin or aspirin decreases sensitivity. Baroreceptor sensitivity is also decreased after endothelial denudation and restored after adding PGI2 back to the denuded sinus suggesting that endothelium is the source of prostanoids that sensitize baroreceptors. Pathologic states such as chronic hypertension and atherosclerosis are associated with both endothelial cell dysfunction and decreased baroreceptor sensitivity. The endothelial cell dysfunction and impairment of prostanoid formation contribute to the decreased baroreceptor sensitivity in these diseases.
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PMID:Paracrine role of prostanoids in activation of arterial baroreceptors: an overview. 177 13

The effects of vitamin D3 on the production of prostacyclin (PGI2) by cultured rabbit vascular smooth muscle cells (VSMCs) were investigated. PGI2 synthesis by VSMCs was significantly increased in the presence of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 1 alpha hydroxyvitamin D3 (1 alpha(OH)D3) at 48 hours [1,25(OH)2D3 greater than 1 alpha(OH)D3]. Physiological concentration of 1,25(OH)2D3 (10(-10) M) significantly increased the synthesis of PGI2. Further, we observed that treatment with 1,25(OH)2D3 significantly induced the activity of cyclooxygenase without changing the activity of phospholipase A2. These findings suggest that the mechanism of action of 1,25(OH)2D3 on the synthesis of PGI2 is mediated by the cyclooxygenase pathway. It seems possible that vitamin D3 is a vasoactive agent and may play a protective role in the development of atherosclerosis.
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PMID:Vitamin D3 stimulates the production of prostacyclin by vascular smooth muscle cells. 177 35

Platelet activity in circulating blood is controlled by platelet-vessel-wall interactions. This includes the generation of endothelium-derived factors, such as the arachidonic acid metabolite prostacyclin and endothelium-derived relaxing factor (EDRF), probably NO, generated from L-arginine. Both compounds inhibit platelet function and are arterial vasodilators. Endothelial dysfunction, e.g. during advanced atherosclerosis, is associated with reduced local formation of these compounds. This may result in platelet hyperreactivity and an increased risk of acute thrombembolic complications. Exogenous administration of synthetic PGI2-mimetics inhibits platelet function. This is a short-term action and the dosage is limited by systemic hypotension. NO-donators (molsidomine, organic nitrates) inhibit platelet-related vasospasm in stenosed coronary arteries in animal experiments. The significance of antiplatelet effects of organic nitrate vasodilators regarding their antianginal effectivity requires further study.
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PMID:[Endothelial factors and thrombocyte function]. 177 33

Altogether 33 patients with insulin-dependent, 51 patients with noninsulin-dependent diabetes mellitus, and 17 patients with atherosclerosis with the affected lower limb major vessels were investigated. The levels of stable forms of prostacyclin I2 and thromboxane A2 were studied with relation to the nature and degree of vascular disorders. Diabetes mellitus and progress of diabetic angiopathies were accompanied by a more pronounced increase in the level of thromboxane B2 and a decrease in the level of 6-ketoprostaglandin F1. An increase in the ratio of thromboxane B2/6-ketoprostaglandin F1 could be interpreted as a prognostically unfavorable sign, suggestive of progression of diabetic angiopathy. It was recommended to study the efficacy and potentialities of correction of disorders with concentrates of ethers of unsaturated fatty acids.
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PMID:[The content of stable forms of prostacyclin I2 and thromboxane A2 in the blood plasma in diabetic angiopathies]. 178 86

Studies, performed in rabbits, examined the effect of feeding a high cholesterol diet and/or a calcium antagonist, nifedipine, on renal microvascular prostacyclin biosynthesis and cholesterol accumulation. After 30 days, cholesterol-fed rabbits had elevated serum and tissue cholesterol levels associated with decreased microvascular prostacyclin biosynthesis and histologic evidence of microvascular and glomerular lipid accumulation. Nifedipine reduced tissue cholesterol levels, enhanced prostacyclin biosynthesis, and reduced the histologic evidence for lipid accumulation in renal microvessels and glomeruli. These studies suggest that calcium antagonists may have a beneficial effect in preventing the tissue cholesterol accumulation associated with a high-cholesterol diet and further suggest that these agents may have beneficial effects in the treatment of renal diseases associated with microvascular or glomerular lipid accumulation.
Atherosclerosis 1991 Dec
PMID:Effect of nifedipine on renal microvascular cholesterol accumulation and prostacyclin biosynthesis in cholesterol-fed rabbits. 178 6


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