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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitroglycerin and the long-acting nitrates are widely used in all of the anginal syndromes and have proven effectiveness in relieving or preventing myocardial ischemia. Recent developments into nitrate mechanisms of action provide new insights as to the many anti-ischemic effects of these agents. Important concepts relating to coronary arterial endothelial function are germane to nitrate therapy. Endothelial-derived relaxing factor (EDRF) is presently believed to be nitric oxide (NO), which exerts vasodilatory and/or antiplatelet actions by increasing intracellular cyclic guanosine monophosphate as a result of activation of the enzyme guanylate cyclase. In the setting of coronary atherosclerosis, or even hyperlipidemia without histologic vascular disease, endothelial dysfunction may be present, promoting a vasoconstrictor/proplatelet aggregatory milieu. Nitroglycerin and the organic nitrates are NO donors; NO is the final product of nitrate metabolism, and in the vascular smooth muscle NO induces relaxation, resulting in vasodilation of arteries and veins. In the presence of inadequate EDRF production and/or release, it appears that nitroglycerin may partially replenish EDRF-like activity. Nitrates have long been known to have major peripheral circulatory actions resulting in a marked decrease in cardiac work. Venodilation and arterial relaxation result in a decrease in intracardiac chamber size and pressures, with a resultant decrease in myocardial oxygen consumption. In addition, a variety of direct coronary circulatory actions of the nitrates have been documented. These include not only epicardial coronary artery dilation, but the prevention of coronary vasoconstriction, enhanced collateral flow, and coronary stenosis enlargement. Recent work suggests that the nitrates may also act by preventing distal coronary artery or collateral vasoconstriction, which can reduce blood flow downstream from a total coronary obstruction. Thus, there are many anti-ischemic mechanisms of action by which nitroglycerin and the organic nitrates may be beneficial in both acute and chronic ischemic heart disease syndromes. The unique salutory effects of the nitrates in subjects with left ventricular dysfunction or congestive heart failure make these drugs particularly attractive for patients with abnormal systolic function and intermittent myocardial ischemia. Finally, the emergent role of intravenous nitroglycerin in acute myocardial infarction offers new prospects that nitrate therapy may prove to be beneficial in acute myocardial infarction as well as postmyocardial infarction for the reduction of left ventricular remodeling.
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PMID:Mechanisms of action of the organic nitrates in the treatment of myocardial ischemia. 152 24

The alterations in the serum lipolytic activity of mice were studied under Uranyl nitrate (UN) intoxication. The lipemia produced as a result of UN intoxication was probed studying the alterations in the serum triacyl-glycerol-hydrolase (EC 3.1.1.3) activity. After an intraperitoneal injection of UN (10 mg/kg and 25 mg/kg), triacyl-glycerol-hydrolase (TAGH) activity was considerably enhanced. In the initiation phase the elevation in the activity was observed to be higher than the elevation in the maintenance phase of acute UN toxicity. The possible reasons for the elevation in the TAGH activity and its role under such intoxication is discussed.
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PMID:Acute toxicity of uranyl nitrate and behaviour of serum lipolytic activity. 409 97

This study was conducted to examine whether nitric oxide regulates lipid metabolism. In Experiment 1, rats were fed for 5 wk diets with or without 0.2 g/kg L-N-nitroarginine (L-NNA), a specific inhibitor of nitric oxide synthase, that were or were not supplemented with 40 g/kg L-arginine. Rats fed L-NNA had significantly higher concentrations of serum triglyceride and total cholesterol, lower concentrations of serum nitrate, and a lower ratio of HDL-cholesterol to total cholesterol than rats fed the basal diet. These alterations were suppressed by supplementing L-arginine to the L-NNA-containing diet. In Experiment 2, rats were fed diets with or without 0.2 g/kg L-NNA. Dietary L-NNA elevated serum concentrations of free fatty acids without affecting those of ketone bodies. L-NNA lowered the activity of hepatic carnitine palmitoyltransferase, the rate-limiting enzyme of fatty acid oxidation, but did not affect activities of hepatic glucose-6-phosphate dehydrogenase and fatty acid synthase which are lipogenic enzymes. These results suggest that the lower nitric oxide level in rats fed L-NNA leads to hyperlipidemia and that the elevation in serum triglyceride might be due to reduced fatty acid oxidation.
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PMID:Feeding rats the nitric oxide synthase inhibitor, L-N(omega)nitroarginine, elevates serum triglyceride and cholesterol and lowers hepatic fatty acid oxidation. 885 18

Our object was to evaluate the effects of regular mild exercise on blood pressure and on circulating level of ouabainlike factors (OLF) and of nitrate anion, an endproduct of nitric oxide (NO) in humans. We measured plasma ouabainlike immunoreactivity (OLI) and nitrate ions (NO3.) before and after mild exercise for 3 months' duration in 16 patients with essential hypertension, diabetes mellitus, obesity, or hyperlipidemia. Plasma OLI was measured using an amplified ELISA system with anti-ouabain antibody and biotinyl-tyramide. Serum NO3. was measured with high-performance liquid chromatography (HPLC) with an anion-exchange column. With the reverse phase HPLC system with an octa decylsilyl silicagel column, the elution volume of plasma OLI of a healthy volunteer matched that of authentic ouabain in a gradient elution system of acetonitrile/H2O. Plasma OLI levels decreased significantly by about 34% after mild exercise, and NO3. levels tended to be within the reference interval in normal volunteers. Body weight, diastolic and systolic blood pressure, serum triglyceride and acetylcholine esterase (a marker of the fatty liver) were significantly decreased (p < 0.01) after 3 months of regular mild exercise. The plasma OLI level was significantly correlated with plasma NO3., there was a trend toward a correlation with diastolic blood pressure (p = 0.06) before and after regular exercise. Regular mild exercise led to a decrease in plasma levels of OLI, and acetylcholine esterase activity and blood pressure in adult patients. Results suggest that changes in OLF production contribute to the blood pressure regulation seen in patients who exercise regularly.
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PMID:Vasodepressor effects of exercise are accompanied by reduced circulating ouabainlike immunoreactivity and normalization of nitric oxide synthesis. 910 42

The prognosis of patients suffering from severe hyperlipidaemia (HLP), sometimes combined with elevated lipoprotein (a) levels, and coronary heart disease (CHD) refractory to diet and lipid lowering drugs is poor. A new therapeutic option for such patients is regular treatment with low density lipoprotein (LDL) apheresis. In total 33 patients (16 males, 17 female, aged 43.8+/-14.3 years), suffering from severe HLP resistant to diet and lipid lowering drugs, were treated for 62.3+/-21.3 (range, 1-113) months with LDL-apheresis. Four different LDL-apheresis systems were used: the dextran sulfate adsorption for 28 of 33 (Liposorber, Kaneka, Japan), immunoadsorption for 2 of 33 (Therasorb, Baxter, Germany), LDL-hemoperfusion for 2 of 33 (Dali, Fresenius, Germany), and the immunoadsorption system with special antilipoprotein (a) columns for 1 of 33 patients (Lipopak, Pocard, Russia). Before applying LDL-apheresis, 27 of 33 patients suffered from CHD with severe angina pectoris symptoms, a history of myocardial infarction or coronary artery venous bypass (CAVB). With LDL-apheresis, reductions (p < 0.05) of 46% for total cholesterol, 49% for LDL, 28% for Lp(a), and 38% for triglycerides were reached. Severe side-effects, such as shock or allergic reactions, were very rare (0.5%). In the course of treatment an improvement in general well-being and increased performance were experienced in 29 of 33 patients. In 23 of 27 patients suffering from CHD, a reduction of 60 to 100% of nitrate medication was observed. Regarding the different apheresis systems used, there were no significant differences with respect to the clinical outcome and concerning total cholesterol, LDL, HDL, and triglyceride concentrations. But, in respect to elevated lipoprotein (a) levels, the immunoadsorption method using special anti-lipoprotein (a) columns seems to be the most effective (-57% versus -25% [Kaneka, p < 0.05] or -23% [Baxter, p < 0.05]). The present data clearly demonstrate that treatment with LDL-apheresis in patients suffering from severe HLP, refractory to maximum conservative therapy, is effective and safe in long-term application.
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PMID:Low density lipoprotein apheresis in treatment of hyperlipidemia: experience with four different technologies. 1091 23

Heme oxygenase-1 (HO-1) is induced by a variety of conditions associated with oxidative stress. We demonstrated that mildly oxidized LDL markedly induces HO-1 in human aortic endothelial and smooth muscle cell cocultures and that its induction results in the attenuation of monocyte chemotaxis resulting from treatment with mildly oxidized LDL in vitro. To elucidate the role of HO-1 in the development of atherosclerotic lesions in vivo, we modulated HO-1 expression in LDL-receptor knockout mice fed high-fat diets. During 6-week high-fat diet trials, intraperitoneal injections of hemin (H group) or hemin and desferrioxamine (HD group) to induce HO-1, Sn-protoporphyrin IX to inhibit HO-1 (Sn group), and saline as control (C group) were performed. Both the H and HD groups showed significantly less mean atherosclerotic lesions in the proximal aorta compared with the C group, whereas the Sn group showed larger lesion compared with the C group. Modulation of HO expression and HO activities were confirmed by Northern blot analysis and HO activity assay. Immunohistochemical studies revealed significant HO-1 expression in atherosclerotic lesions, where oxidized phospholipids also localized. Major cell types expressing HO-1 were macrophages and foam cells in the lesions. HO modulations affected plasma lipid hydroperoxide (LPO) levels and nitrite/nitrate levels. These results suggest that HO-1, induced under hyperlipidemia, functioned as an intrinsic protective factor against atherosclerotic lesion formation, possibly by inhibiting lipid peroxidation and influencing the nitric oxide pathway.
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PMID:Heme oxygenase-1 inhibits atherosclerotic lesion formation in ldl-receptor knockout mice. 1124 66

Effect of coconut protein in rats fed high fat cholesterol containing diet on the metabolism of lipids and lipid peroxides was studied. In addition, effect of coconut protein were compared with rats fed L-arginine. The results indicate that those fed coconut protein and those fed L-arginine showed significantly lower levels of total cholesterol, LDL+ VLDL cholesterol, Triglycerides and Phospholipids in the serum and higher levels of serum HDL cholesterol. The concentration of total cholesterol, triglycerides and phospholipids in the tissues were lower in these groups. There was increased hepatic cholesterogenesis which is evident from the higher rate of incorporation of labeled acetate into free cholesterol. Increased conversion of cholesterol to bile acids and increased fecal excretion of bile acids were observed. Feeding coconut protein results in decreased levels of Malondialdehyde in the heart and increased activity of Superoxide dismutase and Catalase. Supplementation of coconut protein causes increased excretion of urinary nitrate which implies higher rate of conversion of arginine into nitric oxide. In the present study, the arginine supplemented group and the coconut protein fed group produced similar effects. These studies clearly demonstrate that coconut protein is able to reduce hyperlipidemia and peroxidative effect induced by high fat cholesterol containing diet and these effects are mainly mediated by the L-arginine present in it.
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PMID:Hypolipidemic and antiperoxidative effect of coconut protein in hypercholesterolemic rats. 1188 11

Nitric oxide (NO) plays a pivotal role in the pathophysiology of coronary artery disease. The roles of NO are not only physiological but also pathological in the cardiovascular system. An inappropriate release of NO has been linked to the pathogenesis of CAD. The authors investigated whether serum NOx (nitrate and nitrite), a stable end product of NO, level was related to patients with coronary artery disease. The blood chemistry, such as cholesterol, triglyceride, LDL-C, HDL-C and blood sugar, was also measured in comparison with serum NOx. Serum NOx was measured in samples from 20 healthy controls, 20 angina patients without angiographic evidence of coronary lesions (CAG) and 20 angina patients with angiographic evidence of coronary lesions (CAD) by using modified Griess reaction. The mean serum NOx levels in the CAD groups was higher than CAG and control groups (41.3 +/- 5.5, 32.7 +/- 3.9 and 25.7 +/- 3.5 micromol/L, respectively). NOx levels in the CAD group was only significantly higher than the control groups (p < 0.05) but not the CAG groups. There were no significant differences of NOx levels in all age groups. In the CAD group, women showed significantly higher NOx levels than men (64.0 +/- 7.5 and 29.0 +/- 4.7 microl/L, respectively, p < 0.05). Interestingly, the mean serum NOx levels in the CAD groups was significantly higher in a group of abnormal lipid profiles (cholesterol, triglyceride, LDL-C) and blood sugar than in a group of normal profiles. The results suggested that there was an increased NOx levels in patients with coronary artery disease and much higher in patients with multiple underlying conditions such as hyperlipidemia and hyperglycemia. Thus, the measurement of the NOx levels at different times may help to monitor the state and severity of coronary artery disease.
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PMID:Serum nitric oxide levels in patients with coronary artery disease. 1200 15

We have developed a new analysis method for lipoproteins in serum by high-performance liquid chromatography using a sulfopropyl-ligand column with eluents containing magnesium nitrate. The magnesium ion anchors lipoproteins to the ligands on the column gel. Lipoproteins are eluted from the column with a magnesium nitrate concentration gradient and detected by postcolumn reaction using a reagent containing cholesterol esterase and cholesterol oxidase. High-density lipoprotein, low-density lipoprotein, and very-low-density lipoprotein were eluted in order from the column. The within-assay and between-assay coefficients of variation for cholesterol concentration in lipoproteins were 1.1-3.7 and 1.3-5.8%, respectively. The correlation coefficients between the values of total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol obtained by the new method and those obtained by an enzymatic method using an automated chemical analyzer were 0.940, 0.979, and 0.909, respectively. The new method was successfully applied to the analysis of plasma lipoproteins of patients with hyperlipidemia.
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PMID:Analysis method for lipoproteins by high-performance liquid chromatography with sulfopropyl-ligand column and magnesium ion-containing eluents. 1241 48

Metabolic syndrome is a cluster of metabolic abnormalities, including hypertension, hyperlipidemia, hyperinsulinemia, glucose intolerance and obesity. In such lifestyle-related diseases, impairment of nitric oxide (NO) production or bioactivity has been reported to lead to the development of atherogenic vascular diseases. Therefore, in the present study we investigated changes in the NO/cyclic guanosine monophosphate (cGMP) system in aortas of SHR/NDmcr-cp (cp/cp) rats (SHR-cp), a model of the metabolic syndrome. In aortas of SHR-cp, endothelium-dependent relaxations induced by acetylcholine and endothelium-independent relaxations induced by sodium nitroprusside were significantly impaired in comparison with Wistar-Kyoto rats. Furthermore, protein levels of soluble guanylyl cyclase and cGMP levels induced by sodium nitroprusside were significantly decreased. In contrast, protein levels of endothelium NO synthase and cGMP levels induced by acetylcholine were significantly increased, and plasma NO2 plus NO3 levels were also increased. The levels of lipid peroxide in plasma and the contents of 3-nitrotyrosine, a biomarker of peroxynitrite, in aortas were markedly increased. These findings indicate that in the aortas of SHR-cp, NO production from the endothelium is augmented, although the NO-induced relaxation response is impaired. Enhanced NO production may be a compensatory response to a variety of factors, including increases in oxidative stress.
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PMID:Disturbances in nitric oxide/cyclic guanosine monophosphate system in SHR/NDmcr-cp rats, a model of metabolic syndrome. 1618 78


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