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

In this study we have considered the possibility of inducing vascular damage in Yoshida Pittsburg (YOS) rat, an inbred strain which has endogenous hyperlipidemia without vascular atherosclerotic damage. Cholesterol-enriched diet (4% cholesterol plus 1% cholic acid and 0.5% thiouracil) was administered to YOS rats, in order to induce atherogenesis. The results indicate that, despite significant increase in serum (about 2-fold) and aortic tissue cholesterol (about 6-fold), no morphological damage occurred. A reduction in acetylcholine-mediated relaxation (of about 37%) was observed. No inhibition of ATP- or sodium nitrite-induced relaxation, or of contraction induced by norepinephrine was seen. Serum triglyceride concentration did not vary after administration of a cholesterol-enriched diet. Our results suggest that in heritable hyperlipidemic Yoshida rat, after 2 months of cholesterol-enriched diet, despite increased serum cholesterol levels, no atheromatous plaque developed on the aortic wall. Impaired vascular function and reductions in the response to acetylcholine were related to changed endothelial cell function. Administration of a high cholesterol diet to YOS rat may represent a new model of mixed endogenous and exogenous hyperlipidemia that can resemble many human dislipidemic diseases and therefore may become a useful tool for the study of isolated endothelial dysfunction.
Atherosclerosis 1994 Mar
PMID:Effect of cholesterol-supplemented diet in heritable hyperlipidemic Yoshida rats: functional and morphological characterization of thoracic aorta. 801 7

Constriction in response to serotonin is enhanced in the coronary arteries of atherosclerotic monkeys. The main objective of the present study was to determine whether abnormal responses to serotonin in atherosclerosis are reversed following removal of dietary cholesterol. In addition, we examined the effect of an atherogenic diet and reduction in dietary cholesterol on vascular responses to activation of ATP-sensitive K+ channels with aprikalim. Diameters of small coronary arteries were measured on the epicardial surface of the left ventricle in vivo by using stroboscopic illumination synchronized to the heart cycle to visually freeze the motion of the heart. Diameters were measured with a microscope-video system during topical application of two vasoconstrictor agonists, serotonin and the thromboxane mimetic U46619, and the vasodilator agonists aprikalim and nitroprusside. Responses were compared in normal (n = 9), atherosclerotic (n = 14; high-cholesterol diet), and regression (n = 8; high-cholesterol diet followed by normal diet) monkeys. Constriction of coronary arteries in response to serotonin was enhanced in monkeys on an atherogenic diet and was normal in regression monkeys. Vasoconstriction in response to U46619 and vasodilation in response to nitroprusside and aprikalim were not altered by atherosclerosis. Thus, abnormal vascular responses to serotonin in small coronary arteries of atherosclerotic monkeys without morphological evidence of disease can be reversed to normal by reducing dietary cholesterol.
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PMID:Enhanced coronary vasoconstrictive response to serotonin subsides after removal of dietary cholesterol in atherosclerotic monkeys. 819 87

The mechanism of the unimpaired relaxant effect of ATP in the Watanabe heritable hyperlipidemic rabbit aorta was investigated to elucidate the involvement of P2y purinoceptor at the endothelial level during atherosclerosis. Experiments were carried out on isolated thoracic aorta from such rabbits that were 12 months of age. The potent P2y purinoceptor agonist, 2-methylthio-ATP, did not induce any endothelium- or smooth muscle-dependent relaxation, thus excluding any involvement by the P2y purinoceptor. ADP, but not AMP, produced relaxation of the aorta by acting at both endothelial and smooth muscle levels. Adenosine relaxed the vessel by acting only in smooth muscle. The maintained endothelial relaxant effect of ATP and ADP is therefore not due to activation of P1 or P2y purinoceptors but may involve activation of a remodeled purinergic receptor site that emerges with the progression of atherosclerosis. This site is antagonized by methylene blue. The disorganization of the endothelial monolayer observed in the morphological analysis may be related to functional remodeling of the endothelial purinergic activity in atherosclerosis.
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PMID:Atherosclerosis-related remodeling of aortic relaxation to purines in the Watanabe heritable hyperlipidemic rabbit. 835 83

Homocystinuria due to homozygous cystathionine beta-synthase deficiency is an inborn error of metabolism characterized by a high incidence of thrombosis and premature atherosclerosis. We evaluated TXA2 biosynthesis in vivo and several in vitro tests of platelet function in 11 homocystinuric patients and 12 healthy controls. In vitro, patients' platelet aggregation was within control values as were TXB2 formation, fibrinogen binding, and ATP secretion in response to thrombin. In contrast, the urinary excretion of 11-dehydro-TXB2, a major enzymatic derivative of TXA2, was > 2 SD of controls in all patients (1,724 +/- 828 pg/mg creatinine, mean +/- SD, in patients vs. 345 +/- 136 in controls, P < 0.001). The administration to four patients of low-dose aspirin (50 mg/d for 1 wk) reduced metabolite excretion by > 80%. The recovery of 11-dehydro-TXB2 excretion over the 10 d that followed aspirin cessation occurred with a pattern consistent with the entry into the circulation of platelets with intact cyclooxygenase activity. Prolonged partial reduction in the abnormally high excretion of both 11-dehydro-TXB2 and 2,3-dinor-TXB2, was also observed in seven patients who ingested 500 mg daily for 3 wk of the antioxidant drug probucol. These results provide evidence for enhanced thromboxane biosynthesis in homocystinuria and for its partial dependence on probucol-sensitive mechanisms. Furthermore, the elevated TXA2 formation in homocystinuria is likely to reflect, at least in part, in vivo platelet activation.
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PMID:Abnormally high thromboxane biosynthesis in homozygous homocystinuria. Evidence for platelet involvement and probucol-sensitive mechanism. 837 92

Ischemia induced by atherosclerosis is a common cause of organ failure in the elderly. We investigated the effects of in vivo ischemia created by ligation of the internal iliac arteries on the parameters of in vivo infusion cystometry under urethane anesthesia and on in vitro whole bladder contractility of the rat. Bladder weight significantly increased after ischemia for 14 days. Infusion cystometry demonstrated that in the ischemic bladders the capacity increased, the voiding pressure decreased, and the volume of residual urine increased, which resulted in deteriorated voiding efficacy. The in vitro whole bladder contractility to field stimulation, bethanechol, ATP, and KCl was reduced by ischemia. The passive pressure increased as the bladder volume enlarged and the bladder compliance once decreased by ischemia on the 7th day, but increased on the 14th day. In an active volume-pressure relationship study the peak response was decreased by ischemia. The volume at which response reached a peak value shifted to a larger volume 14 days after surgery. In conclusion, ischemia impaired in vivo rat detrusor power to empty. Since detrusor contractility in vitro decreased in response to various kinds of stimulation, this deteriorated bladder function was supposed to be caused by muscle degeneration.
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PMID:Effects of in vivo Ischemia on the infusion cystometry and in vitro whole bladder contractility of the rat. 871 85

Non-insulin-dependent diabetic (NIDDM) patients show a high incidence of cardiovascular disease, with greater risk of recurrent myocardial infarction and a less favourable clinical outcome than non-diabetic patients. The majority of NIDDM patients are treated with sulphonylurea (SU) derivatives. In the 1970's the University Group Diabetes Program concluded that tolbutamide treatment caused increased cardiovascular mortality; the study, which led to curtailment of oral antidiabetic treatment in the USA, was received with scepticism in Europe. Later criticism of its methodology reduced the impact of the study; however, the question of the safety of SU in NIDDM patients with cardiovascular disease has been re-opened in the face of new experimental data. The heart and vascular tissues do have prerequisites for SU action, i.e. SU receptors and ATP-dependent K+ (K+ATP) channels. These channels play an important role in the protection of the myocardium against ischaemia-reperfusion damage, and their closure by SU could lead to amplified ischaemic damage. Here we review evidence from animal and human studies for deleterious SU effects on ischaemia-induced myocardial damage, either by direct action or through diminished cardioprotective preconditioning. Closure of K+ATP channels by SU can lead to reduction of post-infarct arrhythmias; the drug has also been claimed to improve various atherosclerosis risk factors. The evidence for these beneficial effects of SU is also reviewed. We look at the major difficulties that hamper transfer of information from experimental studies to clinical decision-making: a) The affinity of SU for heart K+ATP channels is orders of magnitude lower than for beta-cell channels; is it reasonable to expect in vivo cardiac effects with therapeutic 'pancreatic' SU doses? b) Most studies utilized high doses of acutely administered SU; are effects similar in the chronic steady-state of the SU-treated diabetic patient? c) Convincing SU effects have been demonstrated in acutely induced ischaemia by acutely administering the drug; do such effects persist in the clinical situation of gradually progressive ischaemia? d) Ischaemia and modification of K+ATP channel activity induce complex events, some with opposing effects; what is the net result of SU action, and do different SU derivatives lead to different outcomes? e) In the chronic (and hence clinically relevant) situation, how can direct (deleterious or beneficial) SU effects be separated from beneficial effects mediated by the metabolic action of the drug? Only large prospective clinical studies, making use of advanced technology for assessment of cardiovascular function, can answer these questions. Millions of NIDDM patients are treated with SU derivatives; many are in the age group where cardiovascular risks are extremely high. The question of whether SU derivatives are beneficial or deleterious for these patients must finally be settle unequivocally.
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PMID:Sulphonylurea treatment of NIDDM patients with cardiovascular disease: a mixed blessing? 873 9

Mitochondria in the heart play two roles essential for cell survival: ATP synthesis and maintenance of Ca2+ homeostasis. These two processes are driven by the same energy source, the H+ electrochemical gradient (delta microH). Under aerobic physiologic conditions, mitochondria do not contribute to the beat-to-beat regulation of cytosolic Ca2+, although a Ca2+ transient in mitochondrial matrix has been described. Micromolar increases in mitochondrial Ca2+ concentration stimulate the Krebs cycle and the NADH redox potential and, therefore, ATP synthesis. Trimetazidine has been shown to improve the calcium transient and, in so doing, the overall myocardial energy production. Under pathologic conditions, mitochondrial Ca2+ overload causes a series of vicious cycles that lead to irreversible cell damage. During ischemia, an alteration in intracellular Ca2+ homeostasis occurs and mitochondria are able to buffer cytosolic Ca2+, suggesting that they retain the Ca(2+)-transporting capacity. Accordingly, once isolated, even after prolonged ischemia the majority of the mitochondria are able to use oxygen for ATP phosphorylation. When isolated after reperfusion, mitochondria are structurally altered, contain large quantities of Ca2+, and produce an excess of oxygen free radicals. Their membrane pores are stimulated and the capacity for oxidative phosphorylation is irreversibly disrupted. The role of mitochondrial DNA damage in progressive human diseases such as coronary atherosclerosis is receiving growing interest. The sequence of ischemia and reperfusion, through increased production of oxygen free radicals, causes mitochondrial deletions in several areas of the mitochondrial genome. This cumulative mitochondrial DNA damage is associated with induction of nuclear oxidative phosphorylation gene mRNA. These observations support the hypothesis that mitochondria and mitochondrial DNA damage play important roles in ischemic heart disease.
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PMID:The role of mitochondria in ischemic heart disease. 889 65

There is mounting evidence that antioxidants may help to prevent coronary heart disease and modulate some thrombotic events such a platelet adhesion. However, the effects of antioxidant supplementation on platelet function in vivo are controversial. A double-blind, randomised, placebo-controlled study was performed on 40 healthy volunteers (20-50 years) supplemented daily with vitamin E (300 mg), vitamin C (250 mg) or beta-carotene (15 mg) for 8 weeks. Platelet function was assessed by platelet aggregation induced by ADP, arachidonic acid or collagen, platelet responsiveness to the inhibitor PGE1, beta-thromboglobulin release and ATP secretion. Supplementation with vitamin E resulted in a significant increase in platelet alpha-tocopherol level (+68%) reflecting closely the increase in plasma alpha-tocopherol level (+69%). Platelet function was significantly decreased by vitamin E as revealed by the decreased platelet aggregation in response to ADP and arachidonic acid, the increased sensitivity to inhibition by PGE1, the decreased plasma beta-thromboglobulin concentration and the decreased ATP secretion. Supplementation with vitamin C did not affect platelet function significantly although a trend towards a decreased platelet aggregability and an increased sensitivity to the inhibitor PGE1 were observed. No significant changes in platelet function occurred after supplementation with beta-carotene. In conclusion, supplementation of healthy volunteers with vitamin E decreased platelet function whereas supplementation with vitamin C or beta-carotene had no significant effects.
Atherosclerosis 1997 Jan 03
PMID:The influence of antioxidant nutrients on platelet function in healthy volunteers. 905 Dec 2

Nitric oxide generated from L-arginine is a messenger for cell-to-cell communication. Abnormalities in nitric oxide release have been implicated in diseases ranging from hypertension and atherosclerosis to septic shock and rheumatoid arthritis. We report here the in vivo and in vitro measurements of nitric oxide in the cardiovascular system using a porphyrinic sensor specific for NO. The sensor has a detection limit 10(-9) M, response time of 0.1-10 ms and diameter of 1-20 microns. Protected by an intravenous catheter or Swan-Ganz catheter, the sensor can be implanted into tissues as well as into the blood stream. Nitric oxide concentrations were measured directly in the heart and also in veins and arteries, ranging in diameter from 100 microns to 5 mm. Nitric oxide production was induced by the action of different physical agents (shear stress, stretching) as well as various chemical substances agonists (bradykinin, acetylcholine, ATP).
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PMID:Direct measurement of nitric oxide in the cardiovascular system. 908 50

1. Diadenosine phosphates were isolated from platelets, adrenal gland and autonomic nerves. The presence of diadenosine phosphates in storage pools releasable into the circulation suggests an important role in the control of blood pressure, and potentially to a modulation of the actions of catecholamines. 2. Besides a role of the diadenosine phosphates in platelet aggregation, these agents have potent vasoactive properties. Vasoactive actions of the diadenosine phosphates were demonstrated in numerous vascular models including most of the physiologically important elements of blood pressure regulation. Mostly, the vasoactive action depends on the number of phosphates in the diadenosine phosphates. Vasodilation can be observed in intact vessels after administration of Ap2A, Ap3A and Ap4A whereas contraction is affected by Ap5A and Ap5A and Ap6A. Vasocontraction induced by the diadenosine phosphates in vascular smooth muscle cells is mediated by an increase in intracellular free Ca2+. 3. In vivo, intravenous injection of Ap4A lowers blood pressure whereas injections of Ap5A and Ap6A caused a prolonged increase in blood pressure. In blood, in contrast to ATP, diadenosine phosphates are relatively long-lived molecules, suggesting that the action of the latter is of intermediate time span. In a similar manner to the vasoconstrictor angiotensin II, diadenosine phosphates also act as mitogens. It can be assumed that diadenosine phosphates may be involved in pathophysiological events of circulation including hypertension and atherosclerosis.
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PMID:Vascular actions of diadenosine phosphates. 913 16


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