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

1. The present study was undertaken to examine the effect of the angiotensin converting enzyme (ACE) inhibitor, enalapril, on blood pressure and spontaneous blood glucose levels in two rat models: our new diabetic hypertensive rat in which genetic hypertension and diabetes develop following cross-breeding of Cohen diabetic rat (CDR) and spontaneous hypertensive rats (SHR); and a rat in which hypertension, hyperinsulinaemia and hyperlipidaemia were induced by fructose diet. 2. The new strain of animal was fed the usual copper-poor sucrose diet, and for 4 weeks received enalapril. The fructose-induced hyperinsulinaemic animals were fed a fructose-enriched diet for 3 weeks, and enalapril 20 mg per kg per day was added to the drinking water for 2 more weeks. 3. The new strain of diabetic-hypertensive rats that received enalapril showed a significant decrease in blood pressure level. The fructose-fed animals showed a fall in insulin and blood pressure following the introduction of enalapril to their diet. 4. The present study confirms the advantage of the ACE inhibitor enalapril in improving the metabolic parameters of hypertensive diabetic rats, including insulin sensitivity.
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PMID:Enalapril improves glucose tolerance in two rat models: a new hypertensive diabetic strain and a fructose-induced hyperinsulinaemic rat. 907 25

IgA (immunoglobulin A) nephropathy is the most common form of primary glomerulonephritis worldwide. It generally has a good prognosis, with 15-year rates of kidney survival from the apparent onset of disease usually well in excess of 70%. Progression, when it occurs, is usually a slow, indolent process, and spontaneous remission of disease activity occurs in 7% of patients. It is possible to predict, from the initial presenting features and laboratory findings, renal biopsy and clinical course during follow-up, which patients are likely to have progressive renal disease. Identification of the factors likely to be associated with progression is of importance in helping to establish which patients will benefit from specific therapeutic intervention. For all patients, attention should be directed toward general health issues in an endeavour to reverse factors that are likely to have an adverse impact on renal function. This should include early detection and tight control of hypertension (present in 50% of all patients with IgA nephropathy during the course of their disease), along with utilisation of antihypertensive agents that have specific renoprotective effects, namely ACE inhibitors or calcium antagonists. Such therapy should also be considered in normotensive patients with heavy proteinuria, as a reduction of proteinuria is often achieved by this means. Other aims should include maintenance of desirable bodyweight, correction of hyperlipidaemia, cessation of smoking, participation in an active exercise programme, avoidance of exposure to nephrotoxins and maintenance of a high fluid intake. A low protein/low phosphate diet together with phosphate binder therapy should be commenced early in the course of renal impairment. Corticosteroid and/or cytotoxic drug therapy should be considered in the small percentage of patients with heavy proteinuria or a rapid decline in renal function. Such therapeutic endeavours are likely to delay the onset of renal failure in patients with progressive IgA nephropathy.
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PMID:Recognition and management of IgA nephropathy. 946 91

The generation of nitric oxide by the vascular endothelium maintains a continuous vasodilator tone that is essential for the regulation of blood flow and blood pressure. Nitric oxide also contributes to the control of platelet aggregation and has important antiatherogenic effects. These properties are mediated by the action of constitutive nitric oxide synthase and subsequent activation by nitric oxide of soluble guanylate cyclase. Impaired release of nitric oxide occurs in most animal and human models of hypertension, contributing to the increased peripheral resistance and most likely to the development of cardiovascular complications. Antihypertensive medications (angiotensin-converting enzyme [ACE] inhibitors and calcium channel blockers) appear to prevent the impairment of nitric oxide-mediated vasodilation in experimental hypertension, though in humans the data are not as clear. Reduced nitric oxide release appears therefore to be a consequence rather than a cause of high blood pressure, and the reduction in blood pressure per se is most important. In hyperlipidaemia, endothelium-dependent relaxations are reduced probably due to the inhibitory action of oxidized low-density lipoproteins on endothelium-dependent relaxations. Lipid-lowering strategies and, more recently, ACE inhibition have been demonstrated to improve nitric oxide dependent coronary vasodilation in hypercholesterolaemic patients with and without atheromatous coronary disease. Nitric oxide dependent vasodilation is also impaired in insulin- and non-insulin-dependent diabetes as well as in healthy aging. Endothelial dysfunction may be improved in non-insulin-dependent diabetes by administration of the antioxidants, supporting the hypothesis that nitric oxide inactivation by oxygen-derived free radicals contributes to abnormal vascular reactivity in diabetes.
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PMID:Impairment and restoration of nitric oxide-dependent vasodilation in cardiovascular disease. 948 1

The prevention of coronary artery disease is based on the control of several factors associated with a disease or clinical condition and suspected to play a pathogenetic role, defined as 'risk factors'. Smoking is a powerful risk factor for coronary artery disease, with risk of events increasing in relation to the number of cigarettes smoked daily. Smoking cessation is associated within 3-4 years, with a significant reduction in cardiovascular risk. Hyperlipidaemia is a powerful predictor of coronary disease with a strong, independent, continuous and graded positive association between cholesterol levels and risk of coronary events. Several large studies have shown the benefit of cholesterol reduction, and there is clear evidence of the efficacy of statins in the reduction of events in primary and secondary prevention. Hypertension is a significant, strong and independent risk factor for coronary artery disease morbidity and mortality and the reduction of events and mortality by antihypertensive treatment is well documented. Obesity is associated with an increase in all-cause mortality and cardiovascular mortality, with a particularly high risk for subjects with central obesity. Central obesity is also part of the so-called 'metabolic X syndrome' including insulin resistance, which appears to be associated with a particularly high risk of coronary artery disease. Type 1 and type 2 diabetes mellitus are associated with an increased risk of cardiovascular disease, especially in women. Several studies have shown that good metabolic control and multifactorial risk factor reduction significantly lower the coronary risk in these patients. Recent evidence is accumulating that some clotting factors (fibrinogen, factor VII, von Willebrand factor) and fibrinolytic factors (t-PA and PAI-1) are associated with an increased risk of coronary artery disease. The European Concerted Action on Thrombosis (ECAT) showed that the levels of fibrinogen, von Willebrand factor antigen, and t-PA antigen are independent predictors of subsequent coronary syndromes in patients with angina pectoris, and that low fibrinogen is associated with a low risk of events despite high cholesterol levels. Post-menopausal status is associated with increased risk of coronary artery disease, particularly when menopause is premature (before the age of 45) or abrupt (surgical). There is strong, thought not yet completely definite evidence that post-menopausal hormone replacement therapy may significantly reduce the risk of events and improve survival. Hyperhomocysteinaemia is an emerging risk factor independently associated with an increased risk of coronary artery disease, cerebral vascular disease, and peripheral vascular disease. The administration of vitamin B6, B12 or folate seems to be useful and is currently under further evaluation. Recently, attention has been focused on the correlation between coronary artery disease and genetic factors, such as ACE gene polymorphism or the gene polymorphism for the IIIa-moiety of the platelet fibrinogen receptor IIb-IIIa. In primary prevention, control of the major risk factors mainly in patients with clustered factors will substantially reduce the risk of ischaemic events. Secondary prevention of CHD is based on: aggressive behavioural advice, blood pressure reduction in hypertensives, good metabolic control of diabetes, and cholesterol reduction. Aspirin, beta-blockers, ACE inhibitors, and oral anticoagulants, may be useful in selected patients.
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PMID:Classical risk factors and emerging elements in the risk profile for coronary artery disease. 951 44

There is recent interest in the possibility that angiotensin converting enzyme inhibitors (ACE inhibitors) may reduce the damage inflicted on the arterial wall by common cardiovascular risk factors such as hypertension, hyperlipidaemia and ageing. The efficacy of these drugs in blood pressure reduction is accepted, but whether there is an excess benefit on arterial structure and function, conferred by use of ACE inhibitors over more traditional antihypertensives, is still under debate. There is also evidence in animal models to suggest that ACE inhibition is effective in reduction of arterial damage due to experimental hyperlipidaemia. ACE inhibitors not only reduce the conversion of angiotensin I and angiotensin II, which can interact with the sympathetic nervous system, but also prevent the degradation of bradykinin. This means that ACE inhibitors have several potential mechanisms through which they could suppress intimal hypertrophy and prevent endothelial dysfunction, which is believed to precede arteriosclerosis in man. Although much further work is needed to clarify the mechanism underlying the beneficial effects on the arterial wall of this group of drugs, they do appear to have significant potential in the effort to reduce cardiovascular mortality and morbidity, especially in high risk groups.
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PMID:The impact of angiotensin converting enzyme inhibitors on the arterial wall. 954 23

Circulating soluble E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion molecule-1 (VCAM-1) concentrations were evaluated in 93 nonobese essential hypertensive patients, of whom 16 had impaired glucose tolerance and hyperlipidemia (group I); 25 had impaired glucose tolerance (group II); 28 had hyperlipidemia (group III); and 24 had no metabolic abnormalities (group IV). A group of 22 healthy volunteers served as a control group. All groups were without clinical or ultrasound evidence of vascular lesion and were matched for age, sex, and BMI. Endothelial soluble adhesion molecules were measured at baseline, during an oral glucose tolerance test, and after 12 weeks of either enalapril or placebo treatments. Plasma soluble E-selectin, ICAM-1, and VCAM-1 were higher (P < 0.05) in group I and II than in the other groups (group I: E-selectin, 96.1+/-27.1; ICAM-1, 304.0+/-102.1; VCAM-1, 626.1+/-156.2 microg/l. Group II: E-selectin, 88.0+/-18.0; ICAM-1, 268.0+/-84.1; VCAM-1, 594.1+/-140.9 microg/I. Group III: E-selectin, 70.1+/-18.1; ICAM-1, 195.1+/-68.0; VCAM-1, 495.9+/-110.1 microg/l. Group IV: E-selectin, 65.1+/-16.1; ICAM-1, 168.1+/-64.0; VCAM-1, 472.1+/-108.2 microg/l). Soluble adhesins levels were not higher than normal in groups III and IV. Plasma soluble ICAM-1 concentrations increased in group I after glucose administration and were directly correlated with 2-h insulin levels (r=0.648, P=0.007). Compared with placebo, 12 weeks of enalapril treatment significantly (P < 0.0001) reduced soluble E-selectin, ICAM-1, and VCAM-1. Decrements of soluble adhesins were not dependent on enalapril-related blood pressure changes. Therefore, an early endothelial activation was present in essential hypertensive patients with impaired glucose tolerance, regardless of the presence of hyperlipidemia. ACE inhibition counteracted such endothelial activation.
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PMID:Early activation of vascular endothelium in nonobese, nondiabetic essential hypertensive patients with multiple metabolic abnormalities. 956 1

The renin-angiotensin system is an important modulator of arterial blood pressure and inhibitors of the angiotensin-converting enzyme (ACE-Is) and are currently used in the treatment of hypertension. The pleiotropic actions exerted by angiotensin II (AngII) on the functionality of the vessel wall may have pro-atherosclerotic outcomes; evidence for an anti-atherosclerotic effect of ACE-Is has been presented and an antioxidant effect has been attributed to thiol-containing ACE-Is, like Captopril. The present study has been undertaken to investigate the effect of Delapril, a lipophilic ACE-I, on the development of atherosclerosis in cholesterol-fed rabbits. While it did not correct hyperlipidemia, Delapril dose dependently inhibited the development of atherosclerosis, expressed as aortic area covered by lesions (23.3+/-4.1, 21.3+/-2.4 and 18.5+/-3.3% with Delapril at the daily dose of 5, 10 and 20 mg/kg, respectively, versus 38.2%+/-6.4 for control animals) and its effect was similar to that of Captopril (14.5+/-5.1% at the daily dose of 25 mg/kg). Furthermore, Delapril partially and dose dependently restored endothelium-dependent relaxation, which is impaired in vessels from hypercholesterolemic animals (51.80+/-12.18, 59.74+/-5.16, 69.13+/-8.70 maximal percent relaxation versus 48.26+/-3.05% for the untreated control and 67.67+/-6.72% for Captopril-treated animals). An antioxidant mechanism is unlikely to explain this data, since Delapril does not contain thiol groups. These observations suggest that Delapril may represent an effective pharmacological approach for the treatment of atherosclerosis during its early phases.
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PMID:Delapril slows the progression of atherosclerosis and maintains endothelial function in cholesterol-fed rabbits. 956 38

Essential arterial hypertension is frequently accompanied by metabolic disorders, including hyperlipidemia. In Polish epidemiological studies hyperlipidemia has been detected in 70% of men and 67% of women. Metabolic disorders associated with arterial hypertension increase with the increasing severity of the disease and affect its course. However, hypotensive therapy may modify the metabolic parameters. Therefore, the appropriate antihypertensive therapy should be selected individually taking into account actual metabolic abnormalities. At present it is recommended to use ACE inhibitors, calcium antagonists and alpha-receptor blockers as the first line therapy in patients with arterial hypertension combined with hyperlipidemia.
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PMID:[Antihypertensive drug therapy in relation to lipid disorders]. 969 49

Nephropathy may develop in patients with type 1 diabetes because poor glycemic control produces effects that eventually lead to glomerular scarring and renal failure. The worse and more prolonged the hyperglycemia, the greater the risk of diabetic nephropathy. In patients with type 2 diabetes, hyperglycemia, as well as insulin resistance and generalized vascular disease, is involved in the pathogenesis of nephropathy. The glomerular changes of early diabetic nephropathy can be identified only by renal biopsy or by testing for microalbuminuria. Once macroalbuminuria occurs (albumin excretion rate, > 300 mg/day), usually after type 1 diabetes has been present for 10 to 15 postpubertal years, end-stage renal disease is almost inevitable. However, aggressive control of hypertension in diabetic patients without microalbuminuria helps avoid nephropathy, and tight glycemic control in those with microalbuminuria can avoid or delay its onset. Even when macroalbuminuria is present, treatment can prolong renal function. Aggressive antihypertensive therapy, especially with ACE inhibitors, can reduce renal decline by half. Avoiding circumstances that may damage the kidneys (e.g., use of radiocontrast materials or nephrotoxic drugs, dehydration, hyperlipidemia, urinary tract infection, buildup of AGEs) is critical. Some treatment methods are controversial (dietary protein restriction) or still under investigation (use of injected or oral heparin) but may help delay renal transplantation or dialysis.
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PMID:Dealing with diabetic nephropathy. 1002 5

Both hypertension and diabetes mellitus are multifaceted dynamic expressions of pathophysiological disequilibrium that are closely related with and even intermingled by a number of common factors. Hyperinsulinaemia and insulin resistance may be possible links between hypertension and diabetes mellitus. While working on the effect of different antihypertensive agents in several animal models of simultaneously occurring diabetes-mellitus and hypertension it was found that most antihypertensives prevented streptozotocin (STZ)-induced hypertension in rats. Hydralazine, angiotensin converting enzyme (ACE) inhibitors, calcium channel blockers (CCB) and clonidine prevented STZ-induced cardiomyopathy, hyperlipidaemia and glucose tolerance. It was further demonstrated that atenolol produced many unfavourable effects like hyperlipidaemia and decreased cardiac functions. We also used other animal models of simultaneously occurring diabetes-mellitus and hypertension such as genetically hypertensive or spontaneously hypertensive (SH), Deoxycorticosterone acetate (DOCA)-hypertensive and neonatal streptozotocin-induced NIDDM rats. Results of our studies suggest that SH, neonatal STZ-induced NIDDM, and fructose hypertensive rat models may be considered as models for insulin resistance - the concept that has come into limelight in recent years. DOCA may have some influence on glucose homeostasis and insulin sensitivity and some sort of counteraction to STZ-induced cardiovascular and metabolic changes occur with DOCA. Hence, it may not be considered as an ideal model to study the metabolic and cardiovascular complications of hypertension associated with diabetes-mellitus. Among ACE inhibitors, perindopril, spirapril, and among calcium channel blockers (CCB) used in our study amlodipine and nifedipine were found to produce an increase in insulin sensitivity. Enalapril, ramipril, lisinopril and nitrendipine failed to alter insulin sensitivity as far as the glycaemic control is concerned. Extension of the results of these experiments to the clinical practice substantiated many of the findings and a good correlation between results obtained from experimental studies and clinical data was found.
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PMID:Hyperinsulinemia and insulin resistance in hypertension: differential effects of antihypertensive agents. 1005 52


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