Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experiments were designed to examine the effect of oxidized low density lipoproteins (Ox-LDLs) on the expression and the release of endothelin from cultured endothelial cells and intact blood vessels. Ox-LDLs (30-300 micrograms/ml), but not native low density lipoproteins (200 micrograms/ml), stimulated the expression of preproendothelin mRNA in porcine and human endothelial cells, leading to a time- and concentration-dependent release of the peptide into the culture medium. The Ox-LDL-stimulated release of endothelin was mimicked by acetylated low density lipoprotein and abolished by downregulation of protein kinase C by phorbol ester. In the intact porcine aorta, Ox-LDLs, but not native low density lipoproteins, also increased the release of peptide in an endothelium- and concentration-dependent manner. The maximal effect was observed at a concentration of 100 micrograms/ml. Incubation of the intact porcine aorta with the scavenger receptor antagonist dextran sulfate decreased the formation of endothelium evoked by Ox-LDLs. The Ox-LDL-stimulated production of the peptide was further augmented in the presence of thrombin (4 units/ml) and was unaffected by nitric oxide-generating compound 3-morpholinosydnonimine (10(-5) M). These results suggest that Ox-LDL may be an endogenous mediator of the augmented release of endothelin observed in hyperlipidemia and atherosclerosis. The increased production of the peptide could contribute to vasospastic events and may promote vascular smooth muscle proliferation and progression of atherosclerotic vascular disease.
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PMID:Oxidized low density lipoproteins induce mRNA expression and release of endothelin from human and porcine endothelium. 131 34

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

As a source of several vasoactive factors, the endothelium takes part in the regulation of vascular tone. The most important endothelium-derived vasoactive substances are nitric oxide, prostacyclin, endothelin-1 and contracting factors requiring the activity of cyclooxygenase. The endothelium is an obvious target organ of cardiovascular risk factors. Accordingly, functional alterations do occur with aging, hypertension, and lipids. All three conditions are associated with a decreased basal and stimulated release of endothelium-derived nitric oxide. On the other hand, the release of endothelin-1 appears to increase with age, while the sensitivity to the peptide markedly decreases under the same conditions. In the spontaneously hypertensive rat, acetylcholine and stretch evoke the release of cyclooxygenase-dependent endothelium-derived contracting factor, most likely prostaglandin H2. The sensitivity and circulating levels of endothelin-1, on the other hand, are reduced in this experimental model of hypertension. In the porcine coronary circulation, oxidized low-density lipoproteins selectively reduce endothelium-dependent relaxations to aggregating platelets, serotonin, and thrombin which are mediated by nitric oxide. The alterations of endothelial function occurring with aging, hypertension, and hyperlipidemia may have important clinical implications for the pathogenesis of cardiovascular disease.
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PMID:Endothelium-dependent control of vascular tone: effects of age, hypertension and lipids. 195 6

Temporary changes in audiometry have been reported in hypercholesterolaemia and in hypo- and hyperthyroidism. The purpose of the present prospective and controlled study was to record changes in conduction time of auditory brain-stem response (ABR) in patients with hyperlipidaemia and hypothyroidism before and after therapy over a period of 6 months. The acoustic evoked brain-stem response Jewett waves I-V were delayed in patients with hypercholesterolaemia, hypertrigliceridaemia and hypothyroidism in comparison with an age-matched control group. The changes in pure-tone threshold and brain-stem responses correlated with the degree of hyperlipidaemia or hypothyroidism. After treatment the brain-stem responses of hypothyroid patients tended to return to normal, and in a few cases normal pure-tone thresholds were achieved. Of the patients with hypercholesterolaemia and hypertrigliceridaemia, 28% had improvements in pure-tone thresholds, whereas no significant changes were found in the ABR following therapy.
HNO 1990 Dec
PMID:[Effect of hyperlipidemia and hypothyroidism on auditory evoked brain stem responses]. 208 69

An increased platelet-vessel wall interaction plays an important role in most forms of cardiovascular disease. In healthy arteries, the vascular endothelium prevents platelet adhesion and aggregation. As a mediator of this protective function, the endothelium produces prostacyclin, endothelium-derived nitric oxide and tissue plasminogen activator. Cardiovascular risk factors such as hypertension, hyperlipidemia and diabetes are associated with an increased platelet activation and with decreased antithrombotic properties of the blood vessel wall. The available inhibitors of platelet function interfere only with one of various mechanisms of platelet activation and of the platelet-vessel wall interaction. Prostaglandin inhibitors, such as aspirin and newer, more specific inhibitors, prevent the production and/or the effect of thromboxane A2 on platelets and the blood vessel wall. Other drugs interfere with the effect of adenosine diphosphate on platelets, or they increase intracellular concentration of cyclic GMP or AMP in platelets and vascular smooth muscle cells. The protective effects of platelet inhibitors in primary and particularly in secondary prevention of cardiovascular diseases have been documented in numerous studies. The successful clinical use of these substances, however, requires a selective prescription of the drugs in patients with cardiovascular disease.
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PMID:[Thrombocyte inhibitors in cardiovascular therapy]. 221 49

Endothelial cells can release substances which profoundly affect vascular tone and platelet function. The inhibitory substances include endothelium-derived relaxing factor (EDRF or nitric oxide), prostacyclin and probably an endothelium-derived hyperpolarizing factor. Endothelin is a potent vasoconstrictor peptide released from endothelial cells. Under certain conditions, the endothelium can also produce angiotensin II, thromboxane A2 and a cyclooxygenase-dependent endothelium-derived contracting factor. In normal arteries, the effects of EDRF appear to dominate. In diseased arteries, the release and action of EDRF is impaired and that of endothelium-derived contracting factors is increased. Hyperlipidaemia, atherosclerosis and hypertension reduce endothelium-dependent relaxations. Hypoxia inhibits the release of EDRF and prolonged ischaemia severely impairs the response. Regenerated endothelium at sites of mechanical injury exhibits selective defects in response to aggregating platelets. The more effective release of EDRF in arterial compared with venous bypass grafts further suggests an involvement of the factor in preventing vascular occlusion. Therapeutic interventions with specific drugs and diets can augment the impaired endothelium-dependent relaxation of diseased arteries. Thus, functional changes of the endothelium in coronary artery disease may be an important factor in the development of vasospasm, ischaemia and thrombosis.
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PMID:Endothelium-derived relaxing and contracting factors: potential role in coronary artery disease. 268 Apr 93

Endothelial dysfunction appears to be an early event in most forms of cardiovascular disease. The dysfunction may involve a decreased formation, inactivation, or action of nitric oxide or prostacyclin as well as an increased formation of contracting factors, eg, prostaglandin H2 and endothelin-1. Cardiovascular drugs can improve endothelial function either indirectly through their effects on cardiovascular risk factors, such as hypertension, hyperlipidemia, and diabetes or directly through endothelial actions. Direct and indirect endothelial protective effects of cardiovascular drugs may significantly contribute to normal organ perfusion and a reduced incidence of myocardial infarction, stroke, and renal failure in patients. Endothelium-dependent vascular regulation in health and in various cardiovascular diseases as well as the effects of currently available cardiovascular drugs are reviewed.
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PMID:Possibilities and perspectives of pharmacotherapy for endothelial protection. 792 59

The mechanism by which women in the reproductive age group are protected from developing coronary heart disease (CHD) as compared with men of similar age is not known. To elucidate whether there is a gender difference in the rate of atherosclerosis formation, we investigated the rate of development of atherosclerosis in both male and female rabbits fed an identical diet consisting of 2% cholesterol for 10 and 15 weeks. The extent of atherosclerosis was correlated with the amount of basal and stimulated release of nitric oxide (NO) from endothelium-intact aortic rings obtained from these animals. Under identical dietary conditions, the female rabbits fed a high cholesterol diet (HCD) for 10 weeks developed very little atherosclerosis (10% surface involvement) as compared with male rabbits (42% surface involvement). However, no significant gender differences in atherosclerosis were observed after 15 weeks of the HCD. The serum cholesterol, high and low density lipoprotein (HDL and LDL) cholesterol were similar in animals fed the HCD for 10 and 15 weeks. The basal release of NO from endothelium-intact aortic rings was significantly greater in control females as compared with males. The magnitude of endothelium-dependent relaxation of aortic rings obtained from both male and female rabbits fed the HCD were impaired to a similar extent, and this impairment correlated with the duration of hyperlipidemia but not with the extent of atherosclerosis. The arginine content of aortic rings were not different between males (257 +/- 52 nmol/g wet weight) and females (345 +/- 62 nmol/g wet weight) or between control and hyperlipidemic groups (males 312 +/- 69; females 301 +/- 65 nmol/g wet weight). Although the precise mechanism for the slower rate of development of atherosclerosis in the female rabbits as compared with males is not clear, the greater basal release of NO in females before they were fed a hyperlipidemic diet, as well as other factors, may be involved. The impairment of endothelium-dependent relaxation in hyperlipidemic animals is not due to a decrease in the availability of arginine, the substrate for NO.
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PMID:Gender differences in atherosclerosis: possible role of nitric oxide. 863 95

The kidneys play an important role in the development of cardiovascular risk factors. It is well known that heavy proteinuria can induce hyperlipidemia, the uric acid is elevated in some renal deficiencies and that hypertension develops in most end stage renal diseases. In prehypertensive states, specially in subjects with a family history of hypertension, some hemodynamic changes take place, characterized by an increase in renal vasoconstriction with a reduction in renal plasma flow and an elevation of sodium reabsorption. The mechanisms for these alterations are not well understood, but an increase in intracytosolic calcium in vascular smooth muscle cells, a reduction in vasodilatory substances such as nitric oxide and an increased sympathetic nervous activity have been proposed. In normotensive subjects with two hypertensive parents a reduction in sodium diet, an increase in protein intake or in arginine diet could prevent established essential hypertension from developing. In borderline hypertension an early therapy with low doses of calcium antagonists, ACE inhibition or diuretics could be indicated.
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PMID:Can the kidney prevent cardiovascular diseases? 874 38

During the last decade, our understanding of the role of nitric oxide for central renal functions has greatly been enhanced. We know now that nitric oxide is produced in renal arteries, macula densa, glomeruli, and tubules by different NO-synthases. Nitric oxide contributes to physiological regulation of renal blood flow, renal autoregulation, tubuloglomerular feedback, renin release, pressure natriuresis, and tubular function. The physiological role of nitric oxide can be modulated by a variety of pathophysiological influences, such as dyslipidemia, diabetes mellitus, hypertension, specific drugs, or radiocontrast agents. In this article, the possible interactions between nitric oxide and atherogenic lipoproteins with regard to important renal functions and development of glomerulosclerosis have been stressed. Atherogenic lipoproteins impair endothelium-dependent, nitric oxide-mediated dilations of renal arteries. The underlying mechanism involves formation of reactive oxygen species which inactivate nitric oxide. Lipoproteins induce formation of oxygen radicals not only in arteries, but also in glomeruli and juxtaglomerular cells, causing, e.g., stimulation of renin release. Although interactions between lipoprotein and nitric oxide take place at different levels, they finally may contribute to renovascular hypertension. Future studies will have to prove that treating hyperlipidemia has a positive influence on nitric oxide-mediated renal functions.
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PMID:Impact of nitric oxide on renal hemodynamics and glomerular function: modulation by atherogenic lipoproteins? 881 12


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