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

Postprandial hyperlipidemia is frequently associated with diabetes mellitus and considered to be an independent coronary risk factor. Nitric oxide (NO) is a key regulator of glucose uptake in skeletal muscle. The goal of this study was to examine the effects of chronic in vivo competitive antagonism of NO synthase (NOS) by the administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) on glucose and lipid metabolism in diabetic (Otsuka Long-Evans Tokushima Fatty [OLETF]) and nondiabetic rats. Chronic administration of L-NAME to rats induced reduced NO production and hypertension in both strains of rats. No detectable impairment of plasma levels of postprandial triglyceride (TG) or insulin sensitivity in nondiabetic rats was detected by chronic treatment of L-NAME, but significant impairment was observed in the cases of diabetic rats. These results suggest that diabetes, when associated with endothelial dysfunction, results in greater abnormalities in lipid, as well as glucose metabolism.
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PMID:Chronic feeding of a nitric oxide synthase inhibitor induces postprandial hypertriglyceridemia in type 2 diabetic model rats, Otsuka Long-Evans Tokushima Fatty rats, but not in nondiabetic rats. 1203 22

Modifications by hyperlipidemia of endothelium-dependent and -independent relaxations were evaluated in cerebral and temporal arteries from control and hyperlipidemic (high cholesterol-fed) monkeys. Histologically atherosclerotic lesions were not observed in either group. Relaxations induced by histamine, abolished by N(G)-nitro->L-arginine (>L-NA), were significantly potentiated in the hyperlipidemic monkey cerebral arteries, compared with those in the arteries from control monkeys. Treatment with superoxide dismutase did not affect the histamine-induced relaxation. Conversely, endothelium-dependent relaxations induced by A23187, Ca2+ ionophore, in cerebral arteries did not differ between control and hyperlipidemic monkeys. In temporal arteries, relaxations by acetylcholine and A23187 did not differ between control and hyperlipidemic monkeys. Endothelium-dependent and -independent relaxations by adenosine diphosphate in cerebral and temporal arteries were not affected by hyperlipidemia. Endothelium-independent relaxations by exogenously applied nitric oxide did not differ in the arteries from control and hyperlipidemic monkeys. Nicotine-induced relaxations in cerebral arteries, which were mediated with nitric oxide released from nitroxidergic (nitrergic) nerves, and the contractions caused by nicotine in temporal and mesenteric arteries treated with >L-NA did not differ between control and hyperlipidemic monkeys. It is concluded that long exposure to hyperlipidemia did not affect endothelial functions of monkey middle cerebral and temporal arteries but enhanced nitric oxide-mediated relaxations caused by histamine, possibly due to upregulation of endothelial histamine receptor-mediated functions in the cerebral arteries. The nitroxidergic (nitrergic) and adrenergic nerve functions do not seem to be affected by hyperlipidemia.
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PMID:Endothelial and neuronal functions in cerebral and temporal arteries from monkeys fed a high-cholesterol diet. 1219 32

IRS is a complex disease consisting of a clustering of metabolic disorders, of which hyperglycaemia, hyper-insulinaemia and dyslipidaemia are the most important. Endothelial dysfunction plays an important role in the pathogenesis of atherosclerosis. The effects of hyperinsulinaemia seem to depend on lipidaemia and glycaemia. Hyperglycaemia and hyperlipidaemia have detrimental effects on endothelial function in the fasting as well as the postprandial states. In both situations, the generation of ROS and vasoactive molecules plays a major role in interfering with the atheroprotective endothelium-dependent NO system. Treatment of IRS in regard to endothelial function should be focused initially on lifestyle improvement, such as stopping smoking and eating a balanced diet containing antioxidant vitamins, folic-acid, L-arginine and long-chain omega-3 unsaturated FA. Strict glucose control has shown to improve endothelial function and decrease microvascular complications. However, macrovascular complications, in line with endothelial functional improvement, have so far been reduced only when treatment was focused on other characteristics of the IRS syndrome, in particular dyslipidaemia. Other relevant treatments include ACE inhibitors and thiazolidinediones, and probably tetrahydrobiopterin and folic acid supplementation. Future studies should address the effects of therapeutic neovascularization on endothelial dysfunction.
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PMID:Insulin resistance and vessel endothelial function. 1221 28

We tested the hypothesis that exercise training (Ex) attenuates the effects of hyperlipidemia on endothelial function by enhancing NO-mediated vasorelaxation in porcine brachial (Br) arteries. Adult female pigs were fed a normal-fat (NF) or high-fat (HF) diet for 20 wk. Four weeks after initiation of the diet, pigs underwent Ex or remained sedentary (Sed) for 16 wk. Relaxation to ACh was impaired by HF (P = 0.03). The combination of HF and Sed impaired ACh-induced relaxation more than HF or Sed alone (P = 0.0002). Relaxation to high doses of bradykinin (BK) was impaired by HF (P = 0.0002). Ex significantly improved ACh-induced relaxation (P = 0.01) and tended to improve relaxation to BK (P = 0.38). To determine the mechanism(s) by which HF and Ex affected relaxation to ACh and BK, relaxation was assessed in the presence of N(G)-nitro-l-arginine methyl ester (l-NAME; to inhibit NO synthase), indomethacin (Indo; to inhibit cyclooxygenase), or l-NAME + Indo. In the presence of l-NAME, Indo, or l-NAME + Indo, ACh-induced relaxation was no longer different between HF and NF arteries; however, relaxation remained greater in Ex than in Sed arteries. In the presence of l-NAME or Indo, BK-induced relaxation was no longer altered by HF but was enhanced by Ex. In the presence of l-NAME + Indo, BK-induced relaxation was enhanced by HF and Ex. These data indicate that hyperlipidemia impairs ACh- and BK-induced relaxation by impairing NO- and PGI(2)-mediated relaxation. Ex attenuates the effects of HF by enhancing a vasodilator mechanism independent of NO and PGI(2).
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PMID:Exercise training preserves endothelium-dependent relaxation in brachial arteries from hyperlipidemic pigs. 1267 52

The endothelial cell layer displays the features of a distributed organ and has a variety of biological functions such as keeping the balance between coagulation and fibrinolysis, expression of adhesion molecules for cells in the immune system, metabolism of noradrenaline and 5-hydroxytryptamine, and conversion of angiotensin I and bradykinin. The endothelium also regulates the underlying smooth muscle layer and vascular tone by release of endothelium-derived relaxing factors such as nitric oxide (NO), prostaglandins, and endothelium-derived hyperpolarizing factor (EDHF) as well as vasoconstricting factors such as endothelin, superoxide (O(2)(-)), and thromboxane. We have reviewed the nature, mechanisms of action, and role of these factors in regulation of vascular tone, with special emphasis on NO. By a process catalyzed by NO synthase, NO and citrulline is formed from the substrates molecular O(2) and L-arginine. The main receptor for NO is guanylyl cyclase leading to formation of smooth muscle cyclic guanosinmonophosphate and relaxation. EDHF is an endothelium-derived factor causing vasorelaxation of the underlying smooth muscle layer by hyperpolarization. The nature of EDHF is still unknown, but several candidates for EDHF have been proposed such as potassium ions, hydrogen peroxide, and epoxyeicosatrienoic acids. Prostaglandins such as prostacyclin and prostaglandin E2 binds to specific receptors followed by increases in cyclic adenosinmonophosphate and vasorelaxation, while contractile prostaglandins constrict vessels by activation of thromboxane and endoperoxidase receptors. Superoxide anions induce contraction of vascular smooth muscles cells by scavenging NO. Endothelin is a potent endothelium-derived contractile factor. The synthesis of endothelin-1 is induced by hypoxia, thrombin, interleukin-1, transforming growth factor-beta1, vasopressin, and catecholamines. Cardiovascular risk factors like age, hypertension, and hyperlipidemia are associated with impaired endothelium-dependent vasodilation either as a consequence of increased inactivation of endothelium-derived vasodilators or increased formation of endothelium-derived contracting factors. This imbalance of endothelium-derived factors plays a role for development of atheroslerosis and ischemic vascular diseases.
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PMID:[Role of nitric oxide and other endothelium-derived factors]. 1273 1

Since the rat is an atherosclerosis-resistant species, the study of atherosclerosis using rats is limited. The present study was undertaken to develop an atherosclerotic model in rats, to investigate the effect of nitric oxide (NO) inactivation and hyperlipidemia, and to evaluate the effect of pitavastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) inhibitor, on NO inactivation and on hyperlipidemia-induced changes in the cardiovascular system. Four-month-old male spontaneously hypertensive hyperlipidemic rats (SHHR) and Sprague-Dawley (SD) rats were used to study 1) the effect of the period of treatment with N(G)-nitro-L-arginine methyl ester (L-NAME, 100 mg/L) on high fat diet (HFD)-treated SHHR and SD rats, and 2) the effect of pitavastatin (Pit, 0.3 mg/kg/day) on the changes in the aorta of L-NAME- and HFD-treated SHHR and SD rats. L-NAME administration for 1 month then HFD feeding for 2 months markedly increased the deposition of lipids and the thickness of the endothelium in SHHR. Continuous L-NAME treatment with HFD produced severe injury and stripped of endothelium in both strains. The plasma total cholesterol of L-NAME + HFD-treated and L-NAME + HFD + Pit-treated SHHR was significantly higher than that of control SHHR. Lipid deposition, however, was comparatively less in the aorta of L-NAME + HFD + Pit-treated SHHR. The concentration of cholesterol in the aorta of control SHHR was significantly lower than that in the aorta of L-NAME + HFD-treated SHHR, whereas that of L-NAME + HFD + Pit-treated SHHR was the same as that in control SHHR. These data indicated that Pit blocked lipid deposition in the aorta of L-NAME + HFD treated SHHR without changing plasma lipid profiles. In conclusion, NO inactivation and HFD induce lipid deposition in the endothelium, and the HMG-CoA reductase inhibitor blocks the deposition in SHHR.
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PMID:Anti-lipid deposition effect of HMG-CoA reductase inhibitor, pitavastatin, in a rat model of hypertension and hypercholesterolemia. 1496 17

Asymmetric dimethylarginine (ADMA), a guanidino-substituted analogue of L-arginine, is a potent endogenous competitive inhibitor of the endothelial nitric oxide synthase and therefore a potentially atherogenic amino acid. Hyperlipidemia and hyperhomocysteinemia have both been reported to be associated with elevated ADMA concentrations. Therefore, we investigated the influence of micronized fenofibrate (200 mg/day, 6 week treatment) on the L-arginine:ADMA ratio in 25 hypertriglyceridemic men. ADMA was neither associated to serum triglycerides, serum cholesterol, LDL-cholesterol or HDL-cholesterol or plasma total homocysteine at baseline. Treatment with fenofibrate did not alter plasma ADMA level, in contrast to serum triglycerides which were significantly lowered and plasma total homocysteine which was significantly increased. In addition, serum L-arginine levels significantly increased, leading to a higher L-arginine:ADMA ratio after treatment. The null effect of fenofibrate on plasma ADMA levels is in line with reported effects of other lipid-lowering agents (HMG-CoA-reductase inhibitors), but fenofibrate treatment elevated the plasma L-arginine:ADMA ratio, suggesting an improvement of endogenous NO formation and endothelial function. The results do not support the view that in vivo ADMA metabolism itself is directly influenced by cholesterol or homocysteine.
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PMID:Fenofibrate increases the L-arginine:ADMA ratio by increase of L-arginine concentration but has no effect on ADMA concentration. 1506 97

Male albino rats were given ethanol (3.76 g/kg body weight/day) to induce hyperlipidemia. The rats showed increased concentration of cholesterol and triglycerides in the serum and tissues. Inclusion of coconut protein and L-arginine into ethanol fed rats produced lower levels of total cholesterol, LDL+ VLDL cholesterol, triglycerides and atherogenic index in the serum. Concentration of tissue cholesterol and triglycerides was also lower in these groups. Administration of coconut protein and L-arginine in the ethanol fed rats caused decreased activity of HMG-CoA reductase in the liver and increased activity of lipoprotein lipase in the heart. The activities of malic enzyme and glucose-6-phosphate dehydrogenase were also lower in these groups. Feeding coconut protein and L-arginine in ethanol treated rats showed increased concentration of hepatic bile acids and fecal excretion of neutral sterols and bile acids. All these effects were comparable in rats fed coconut protein and those fed L-arginine. These observations indicate that the major factor responsible for the hypolipidemic effect of coconut protein is due to the high content of L-arginine.
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PMID:Influence of coconut kernel protein on lipid metabolism in alcohol fed rats. 1527 81

Congenital leptin deficiency is a rare, but treatable, cause of severe early-onset obesity. To date, two United Kingdom families of Pakistani origin carrying a frameshift/premature stop mutation, c.398delG (Delta133G), and one Turkish family carrying a missense mutation, c.313C>T (Arg(105)Trp), have been described. Affected subjects are homozygotes and manifest severe obesity and hyperphagia accompanied by metabolic, neuroendocrine, and immune dysfunction. The effects of recombinant leptin therapy have been reported in three children with the Delta133G mutation, and in all cases this has led to a dramatic resolution of clinical and biochemical abnormalities. We now report a Canadian child, of Pakistani origin but unrelated to the previously reported subjects, presenting with severe hyperphagia and obesity, who was found to be homozygous for the Delta133G mutation. In this child, 4 yr of therapy with sc injections of recombinant leptin provided additional evidence for the sustained beneficial effects of leptin replacement on fat mass, hyperinsulinemia, and hyperlipidemia. In addition, leptin administration corrected abnormal thyroid biochemistry and allowed the withdrawal of T(4) treatment, providing additional support for the role of leptin in the regulation of the human hypothalamic-pituitary-thyroid axis.
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PMID:Congenital leptin deficiency due to homozygosity for the Delta133G mutation: report of another case and evaluation of response to four years of leptin therapy. 1547 69

Hyperhomocyst(e)inemia is associated with an increased risk for atherosclerotic disease and venous thromboembolism. The impact of elevated plasma homocysteine levels seems to be clinically relevant, since the total cardiovascular risk of hyperhomocyst(e)inemia is comparable to the risk associated with hyperlipidemia or smoking. There is substantial evidence for impairment of endothelial function in human and animal models of atherosclerosis, occurring even before development of overt plaques. Interestingly endothelial dysfunction appears to be a sensitive indicator of the process of atherosclerotic lesion development and predicts future vascular events. NO is the most potent endogenous vasodilator known. It is released by the endothelium, and reduced NO bioavailability is responsible for impaired endothelium-dependent vasorelaxation in hyperhomocyst(e)inemia and other metabolic disorders associated with vascular disease. Substances leading to impaired endothelial function as a consequence of reduced NO generation are endogenous NO synthase inhibitors such as ADMA. Indeed there is accumulating evidence from animal and human studies that ADMA, endothelial function and homocyst(e)ine might be closely interrelated. Specifically elevations of ADMA associated with impaired endothelium-dependent relaxation were found in chronic hyperhomocyst(e)inemia, as well as after acute elevation of plasma homocyst(e)ine following oral methionine intake. The postulated mechanisms for ADMA accumulation are increased methylation of arginine residues within proteins, as well as reduced metabolism of ADMA by the enzyme DDAH, but they still need to be confirmed to be operative in vivo. Hyperhomocyst(e)inemia, as well as subsequent endothelial dysfunction can be successfully treated by application of folate and B vitamins. Since ADMA seems to play a central role in homocyst(e)ine-induced endothelial dysfunction, another way of preventing vascular disease in patients with elevated homocyst(e)ine concentrations could be supplementation with L-arginine to reverse the detrimental effects of ADMA.
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PMID:Asymmetric dimethyl-L-arginine (ADMA): a possible link between homocyst(e)ine and endothelial dysfunction. 1572 Feb 2


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