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

Twenty necroptic atherosclerotic aortas were studied using a modified en face Hautchen preparation method. Endothelium of 1 x 1 cm pieces of aortas was frozen onto slides with the help of dry ice. Endothelial cells on atherosclerotic lesions were irregularly oriented, had ununiform shape and giant multinucleated endothelial cells were present. The endothelial pavement on atheromatous lesions was usually defective. There was increased activity of ATPase and 5'Nase in endothelial cells on atherosclerotic lesions and on their borders. It is suggested that the high activity of ectonucleotidases of the endothelium on atherosclerotic lesions results in rapid dephosphorylation of ATP and ADP released by platelets aggregating to adenosine. Adenosine accumulated in the unstirred layer of plasma in the macrovasculature can effectively inhibit platelet aggregation and subsequent thrombosis on pathologically changed vascular pavement in atherosclerosis.
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PMID:Activity of ATPase and 5'nucleotidase in endothelium of human atherosclerotic aortas. 130 20

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 normal control of coronary blood flow is through alterations in the resistance of the intramyocardial arterioles (R2). Myocardial cellular hypoxia causes increased breakdown of ATP (or decreases synthesis) resulting in increased concentrations of the purine metabolite, adenosine. This potent endogenous, vascular smooth muscle relaxant vasodilates the R2 arterioles increasing coronary blood flow and myocardial O2 delivery. This mechanism autoregulates coronary blood flow according to myocardial O2 needs. Myocardial hypertrophy (from chronic hypertension) or coronary atherosclerosis interfere with this process and result in myocardial ischemia which may cause symptoms (angina), signs (ECG changes, regional muscle dysfunction) or tissue death (myocardial infarction). In addition, coronary atheroma disrupt endothelial function in the large R1 coronary arteries predisposing to vasoconstriction, platelet aggregation and thrombosis. Therapeutic measures for controlling ischemia may include decreasing oxygen demand (especially heart rate) and maintaining supply (R1 vasodilators and anti-thrombotic drugs such as non-steroidal anti-inflammatories). Intravenous, most inhalational and regional anesthesia appear to interfere minimally in the control of both the normal and ischemic coronary circulation. Thus optimizing myocardial oxygen balance (maintaining supply and decreasing demand) during anesthesia protects the ischemic myocardium. High doses of isoflurane, sevoflurane or desflurane are potent R2 coronary vasodilators which may cause redistribution of collateral blood flow away from ischemic regions (coronary steal). However, if tachycardia and hypotension are avoided, such an effect has not been shown experimentally or clinically. Preliminary evidence suggests that halothane may preferentially dilate R1 arteries and/or interfere with platelet aggregation. If these effects are confirmed, then halothane may prove to be the anesthetic of choice in the non-failing ischemic heart.
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PMID:Physiology, pathophysiology and pharmacology of the coronary circulation with particular emphasis on anesthetics. 164 43

Intravascular thrombus formation in association with lipid depositions in the arterial wall is thought to be involved in the process of atheroma formation. We have previously shown the beneficial effect of palm oil on the serum lipid profile resulting in a lowering of serum triacylglycerol and an elevation of the HDL/LDL ratio. The present study investigates the effect of dietary palm oil on the biochemical parameters associated with clotting and platelet aggregation in young rats (70 g body wt) fed a palm oil diet over a period of 10 weeks. Palm oil-fed rats showed significantly lower levels of fibrinogen and serum lipid peroxide and elevated AtIII levels resulting in a prolongation of clotting time. Reduced platelet aggregation and ATP release associated with a prolongation of bleeding time were also found. These findings, together with our earlier findings on the effect of palm oil on the serum lipid profile, suggest that dietary palm oil may be antithrombotic as well as beneficial in preventing the deposition of lipids on the vessel wall and may, therefore, be protective against the development of atherosclerosis.
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PMID:Effects of dietary palm oil on serum lipid peroxidation, antithrombin III, plasma cyclic AMP, and platelet aggregation. 164 20

Characterization of P2-purinoceptor subtypes has facilitated understanding of the many diverse effects produced by purine nucleotides. P2X-Purinoceptors are located on vascular smooth muscle where they mediate vasoconstriction resulting from ATP released as a cotransmitter with noradrenaline from sympathetic nerves. P2Y-Purinoceptors are usually located on the vascular endothelium where they have a role as mediators of vascular relaxation by locally produced ATP. In some vessels, P2Y-purinoceptors are also located on the smooth muscle, perhaps in association with purinergic or sensory nerves, where they can elicit direct relaxation to neuronally released ATP. The net effect of ATP and its analogues on isolated vessels or on vascular beds will be the results of actions mediated by P2X- and P2Y-purinoceptor subtypes, although changes in vascular tone and in integrity of nerves and endothelial cells may alter the balance of the response. Such changes have been observed in diseased states (e.g., atherosclerosis) and may have important implications for the involvement of P2-purinoceptors in, for example, vasospasm. The development of selective and potent antagonists to P2X- and P2Y-purinoceptors has so far remained elusive, and their therapeutic potential can only be guessed.
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PMID:Roles of P2-purinoceptors in the cardiovascular system. 164 96

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

Serum and aortic tissue cholesterol levels in parallel with aortic relaxation to endothelium-dependent and independent drugs were determined in Watanabe heritable hyperlipidemic (WHHL) rabbits in comparison with New Zealand (N.Z.) normocholesterolemic rabbits, aged 4-14 months. Serum cholesterol was elevated (626 +/- 99 mg/100 ml) in 4-6-month-old WHHL rabbits and significantly lower in 12-14-month-old animals (344 +/- 51 mg/100 ml). Cholesterol infiltration in thoracic aorta was high in young WHHL compared with N.Z. rabbits (0.88 +/- 0.3 mg/100 mg fresh tissue vs. 0.08 +/- 0.003 mg/100 mg, respectively) and it did not vary with age. In N.Z. rabbits, serum and aortic cholesterol levels were low from 4 to 14 months of age. The aortic relaxation to acetylcholine (0.03-3 microM) on EC50 noradrenaline precontracted rings was similar in 4-6-month-old WHHL and N.Z. rabbits of the same age. In WHHL rabbits, the relaxation to acetylcholine was significantly reduced in 7-11- (-35% at maximum) and in 12-14-month-old rabbits (-40% at maximum). In N.Z. rabbits the response to acetylcholine was not modified in the 3 age groups. The relaxation to ATP (30 microM to 3 mM) was reduced by age both in N.Z. and in WHHL rabbits, but in 12-14-month-old WHHL rabbits the maximal relaxing response was significantly more elevated than in age-matched N.Z. rabbits (50.1 +/- 2.5% vs. 35.1 +/- 3.2%, respectively). The aortic relaxation to NaNO2 (10 microM to 3 mM) was reduced by age both in N.Z. and in WHHL rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1991 Aug
PMID:Aortic response to relaxing agents in Watanabe heritable hyperlipidemic (WHHL) rabbits of different age. 179 50

In the present study: (a) physiopathology, (b) clinics, and (c) therapy of cardiothyreosis are discussed. (a) The hyperkinetic syndrome, the earliest clinical sign in thyrotoxicosis (vasodilatation, increase in inotropism, automatism, etc.), is mediated by a two-fold increase in the number of beta-receptors, and supported by an adequate synthesis of ATP and creatinphosphate (CP) in the young and, to a lesser extent, in the elderly. Genetical heart reserves are mobilized, thus significantly increasing the number and the size of mitochondria and also the enzymatic equipment (such as: the alpha-glycerophosphate-dehydrogenase, malic, pentosic cycles, etc.), a.s.o. Due to an excessive adrenergic action (glycogenolysis, an excessive oxygen consumption, up to necrosis, the ATP and CP syntheses dramatically drop; the phosphorus/oxygen ratio decreases to 2 (normal = 4). In this condition, the high functional cardiovascular performances are also impaired (the submaximal effort capacity is attained at a smaller and smaller oxygen consumption; Propranolol 2 mg i.v. decreased the cardiac output by above 30% (vs 10%--normal); electrocardiogram presents aspects of "coronary disease", tachycardia, etc.). An ultrastructural damage occurs: from "mitochondrial disease", partial lysis of myofibrils, to myofibrosis (revealed postmortem), in spite of a reduced degree of coronary atherosclerosis. Ultrastructural and biochemical experimental data support this point of view. (b) The incidence, precocity and severity of the thyrotoxic heart increase with age and the existence of a previous cardiovascular pathology. Cardiothyreosis is not present under 27 years; in 4,353 patients its incidence is of 25% (arrhythmia--21%, heart failure--12%, coronary insufficiency--1-3%). Of a major interest are tachyarrhythmias which may lead to a high mortality by hypodiastolic congestive heart failure, heart failure with secondary hyperaldosteronism, thromboembolic episodes and ventricular fibrillation. Thyrotoxicosis favours the disease of papillary muscles--mitral prolapse and insufficiency, reversible especially in children. (c) The treatment of thyrotoxic heart is an etiologic one (medical, surgical, radioactive--the last two being preferable after the adequate medical therapy). In particular, cardiothyreosis requires a reinforced irradiation (10,000 rads instead of 7,000 rads) in smaller 131I doses. The protection against the increased nocivity of catechols in thyrotoxicosis is very important (which explains the high mortality in the thyrotoxic "storm") and requires propranolol; doses above 2 mg/kilo body/day are recommended. In the elderly, the sensitivity to propranolol decreases: verapamil i.v. is more efficient in paroxysmal tachyarrhythmias (flutter, atrial fibrillation) and in those occurring intra-operatively during halothane narcosis. The anticoagulant therapy is administered in tachyarrhythmias with high ventricular rate, especially in the elderly, to avoid the embolic risk, higher in defibrillation condition.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cardiothyreosis. 182 Oct 70

It is well established that cardiac dysfunction independent of atherosclerosis develops in both humans and animals with diabetes mellitus. The etiology is complex, involving many different processes, one of which may be increased fatty acid utilization and/or a concomitant decrease in glucose utilization by the diabetic heart. We compared control and 6-wk streptozotocin (STZ)-induced diabetic isolated working rat hearts and were able to demonstrate cardiac dysfunction in the diabetic as assessed by depressed heart rate (HR), heart rate peak systolic pressure product (HR.PSP), left ventricular developed pressure (LVDP), and rate of pressure rise (+dP/dt). Paralleling depressed cardiac function in the diabetic were hyperglycemia, hyperlipidemia, and decreased body weight gain compared with age-matched controls. The addition of free fatty acids, in the form of 1.2 mM palmitate, to the isolated working heart perfusate had no effect on either control or diabetic heart function, with the exception of a depressive effect on +dP/dt of diabetic hearts. But diabetic hearts perfused with palmitate-containing perfusate plus the glucose oxidation stimulator dichloroacetate (DCA) showed a marked improvement in function. HR and HR.PSP in spontaneously beating hearts, as well as LVDP and +dP/dt in paced hearts were all restored to control heart values in diabetic hearts perfused in the presence of DCA. Creatine phosphate and ATP levels were similar under all perfusion conditions, thus eliminating energy stores as the limiting factor in heart function. Results indicate that DCA will acutely reverse diabetic cardiac function depression. Therefore glucose oxidation depression in the diabetic heart may be a significant factor contributing to cardiac dysfunction.
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PMID:Effects of free fatty acids and dichloroacetate on isolated working diabetic rat heart. 192 88

Recently published results provide evidence of the importance of oxidatively modified LDL in the development of atherosclerosis. Several typical characteristics of this disease can be ascribed to the effects of oxidized LDL on the different cells involved in lesion formation. In various cell culture systems oxidized LDL was found to be cytotoxic. Therefore we were interested in its influence on parameters of energy metabolism such as glycogen and ATP content as determined for aortic segments in vitro. The results show that oxidized LDL leads to sharp decreases in both parameters, indicating an activation of cellular energy metabolism. Findings obtained from contraction experiments in which oxidized LDL shows a concentration-enhancing effect on arterial segments suggest that the oxidized lipoprotein facilitates cellular Ca2+ liberation. This seems to be a common signal leading to its effects on energy metabolism and contraction and could also explain its cytotoxicity if cells are exposed to it for longer periods.
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PMID:The influence of oxidatively modified low density lipoprotein on parameters of energy metabolism and contractile function of arterial smooth muscle. 207 Oct 25


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