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)

After a brief synopsis of the classical antihypertensive drugs a survey is given of the newer therapeutics, such as calcium antagonists, ACE-inhibitors and alpha 1-adrenoceptor antagonists. Experimental drugs, such as imidazoline receptor agonists, renin inhibitors, angiotensin II receptor antagonists, alpha 2-adrenoceptor antagonists, potassium channel openers, ketanserin, endopeptidase inhibitors, and hybrid (multifactorial) drugs are discussed, with special attention for their modes of action. In spite of the ever increasing number of antihypertensive drugs and principles, the large scale of clinical evidence for a beneficial effect of long-term treatment (in particular with respect to protection against stroke) remains limited to diuretics and beta-blockers. In spite of this limitation it seems worthwhile to consider the newer antihypertensive drugs as well, especially for optimal treatment of the individual patient. The newer drugs may in particular offer special advantages in the presence of concomitant diseases, such as diabetes mellitus, hyperlipidaemia, angina pectoris or congestive heart failure.
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PMID:New avenues in antihypertensive drug treatment. 826 86

Many of hypertensive individuals have glucose intolerance and dyslipidemia, and insulin resistance is common disorder on the basis of these diseases. It is important to take care of these metabolic disease for not only the control of hypertension, blood glucose and hyperlipidemia, but also the prevention of atherosclerosis. We reviewed the effects of angiotensin II receptor antagonists on insulin resistant syndrome.
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PMID:[The effects of angiotensin II receptor antagonists on insulin resistance]. 1036 53

Essential hypertension is frequently associated with the metabolic abnormalities of insulin resistance and dyslipidemia. This prevalent clustering of multiple cardiovascular risk factors may help explain the less-than-expected improvement in coronary heart disease mortality provided by simple blood pressure reduction alone. Many antihypertensive medications effectively reduce blood pressure while providing no benefit or even causing a detrimental effect on the associated metabolic abnormalities. beta-Blockers and diuretics tend to negatively affect both glucose tolerance and plasma lipids. Calcium channel blockers, angiotensin converting enzyme inhibitors, and angiotensin II receptor blockers are most often found to be metabolically neutral. alpha-Blockers provide the most favorable metabolic effects of antihypertensive agents by improving both insulin sensitivity and dyslipidemia. The multiple physiologic mechanisms by which blood pressure medications alter plasma lipids are discussed in detail. The effects of antihypertensive medications on postprandial lipid metabolism and the associated postprandial lipemia-induced endothelial dysfunction deserve special attention.
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PMID:Mechanism of differential effects of antihypertensive agents on serum lipids. 1098 Nov 72

The beneficial effects of anti-hypertensive agents on the cardiovascular system can be counterbalanced by the induction of metabolic disorders, such as hyperlipidaemia. The present trial evaluated the effect of the angiotensin II receptor antagonist, valsartan, on the lipid profile and glucose metabolism in patients with mild-to-moderate hypertension. This was a multicentre, randomized, double-blind, placebo-controlled study with a 3-week dietary run-in period under placebo; thereafter, patients received either valsartan 80 mg orally once daily or placebo for 12 weeks. A total of 123 patients were randomized, of whom 112 patients completed the study. Valsartan significantly lowered systolic blood pressure by 14.1 +/- 12.8 mmHg and diastolic blood pressure by 9.0 +/- 6.6 mmHg. In the placebo group, the corresponding values were 7.8 +/- 14.9 mmHg and 6.2 +/- 7.3 mmHg, respectively. Additionally, in the valsartan group, there was a significant decrease in levels of both low-density lipoprotein (LDL) cholesterol (valsartan, -6.3 +/- 24.9 mg/dl; placebo, +4.2 +/- 27.0 mg/dl) and total cholesterol (valsartan, -7.1 +/- 28.1 mg/dl; placebo, +6.0 +/- 29.4 mg/dl) in comparison with placebo. No significant changes were observed in the levels of triglycerides, high-density lipoprotein cholesterol, very low-density lipoprotein (VLDL) triglycerides, VLDL cholesterol and apolipoprotein B after valsartan treatment. No effect of valsartan was found with respect to fasting plasma glucose and glycosylated haemoglobin levels. Valsartan therapy was safe and well tolerated in our patient population. In conclusion, in addition to the marked decrease in blood pressure, valsartan significantly reduces total and LDL cholesterol levels and is neutral on glucose metabolism.
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PMID:Effect of the angiotensin II receptor antagonist valsartan on lipid profile and glucose metabolism in patients with hypertension. 1167 99

Long considered independent risk factors for end-stage vascular disease, hypertension and atherosclerosis may be intimately linked through their effects on vascular endothelial dysfunction, which are mediated by the renin-angiotensin system (RAS). Angiotensin II, a potent vasoconstrictor and the principal active peptide of the RAS, can also produce structural changes in the vessel wall associated with atherosclerosis. The role of RAS in the pathogenesis of atherosclerosis is supported by several lines of evidence, including the presence and upregulation of angiotensin-converting enzyme (ACE) and angiotensin II in the walls of atherosclerotic arteries. This article reviews recent research showing that administration of the angiotensin II type 1-receptor blocking agents (ARB) losartan and olmesartan medoxomil to cynomolgus monkeys with diet-induced hyperlipidemia prevents the progression of atherosclerosis. Since these effects have been achieved without altering blood pressure or plasma cholesterol levels significantly, it is suggested that these novel effects of angiotensin II receptor blocker treatment may extend the therapeutic profile of this class of agents in the prevention of human vascular disease.
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PMID:Use of angiotensin II receptor blockers in animal models of atherosclerosis. 1182 74

In recent years several multicentric prospective studies have demonstrated the efficacy of some therapeutic measures to slow the progression of renal diseases. Inhibition of renin-angiotensin system (RAS) both by ACE inhibitors (ACEI) and angiotensin II receptor antagonists (ARA) is probably the strongest therapeutic alternative: The antiproteinuric effect of these drugs is an excellent surrogate marker and a predictor of the beneficial influences on the progression of renal failure. The type of renal disease, an inadequate control of blood pressure, and the presence of obesity may counteract the beneficial influences of RAS inhibition, whereas early treatment of all patients with significant proteinuria before the appearance of renal insufficiency and combined therapy with an ACEI and an ARA may augment it. Dietary protein restriction is a classic treatment of chronic renal insufficiency whose effectiveness has been validated by multicentric studies. However, a poor compliance of the patient and the risk of malnutrition with very strict protein restriction could limit the benefits of this treatment. Treatment of hyperlipidemia, prevention of obesity, avoidance of smoking, and regular physical exercise are interventions whose therapeutic potential is progressively recognized, particularly in type 2 diabetic nephropathy. Early correction of anemia may contribute to the slowing of renal disease progression. Although further studies are required, the accumulated evidence and the likelihood of additive beneficial effect of these therapeutic measures advise their combined implementation in patients with chronic renal diseases.
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PMID:Slowing the progression of renal failure. 1198 7

To evaluate the efficacy of angiotensin II receptor blockers (ARBs) for use in the treatment of diabetic nephropathy, we examined the effects of olmesartan medoxomil (olmesartan), an angiotensin II type 1 (AT1) specific ARB, on the progression of nephropathy in Zucker diabetic fatty (ZDF) rats, an animal model of type 2 diabetes. We used 2 doses of olmesartan, a sub-antihypertensive dose and an antihypertensive dose, to specifically examine whether the drug exerts beneficial effects on the kidney without lowering blood pressure. Olmesartan mixed in the diet at a concentration of 0.001% (approximately 0.6 mg/kg/day) or 0.01% (approximately 6 mg/kg/day) was administered for 19 weeks starting from 12 weeks of age, when the animals developed microalbuminuria. Lean non-diabetic rats served as controls. ZDF rats had hyperglycemia, hyperinsulinemia, and moderate hypertension as compared to lean control rats. Plasma glucose and insulin concentrations were not affected by olmesartan, and blood pressure was lowered only by the high dose of olmesartan. Progressive proteinuria in ZDF rats was greatly (about 70%) suppressed by the high dose of olmesartan and moderately (about 30%) suppressed by the low dose that did not significantly lower blood pressure. ZDF rats exhibited hyperlipidemia and hypoalbuminemia, both of which were substantially corrected by treatment with olmesartan. The histological evidence of glomerular and tubular damage in the ZDF rats was also reduced by the drug. These results indicate that AT1 receptor blockade with olmesartan retards the progression of nephropathy associated with type 2 diabetes without affecting glucose metabolism, and that this renal protective effect is at least partly independent of the antihypertensive effect of the drug.
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PMID:Renoprotective effects of blockade of angiotensin II AT1 receptors in an animal model of type 2 diabetes. 1204 43

Aging is accompanied by a progressive and irreversible non-enzymatic modification of protein by carbohydrates, eventually yielding the advanced glycation end products (AGEs). Age generation (Maillard reaction) is markedly augmented in diabetes with sustained hyperglycemia but also in normoglycemic uremia and atherosclerosis. Recent studies have brought new insights into broad derangements in non-enzymatic biochemistry involving not only carbohydrates but also lipids, present in diabetes, uremia, and atherosclerosis. The latter have in common increased levels of reactive carbonyl compounds (RCOs) with attendant protein modifications ("carbonyl stress"). Carbonyl stress might be derived from 1) hyperglycemia (lipemia), 2) oxidative stress, and/or 3) impaired detoxification of RCOs. Manipulation of carbonyl stress in diabetes, uremia and atherosclerosis opens new therapeutic approaches including redox modulation, RCO detoxification, and carbonyl stress inhibition. The first generation of carbonyl stress inhibitors such as aminoguanidine trap RCOs with its hydrazine group. Unfortunately, aminoguanidine (AG) traps pyridoxal as well as noxious RCOs, so that its long-term administration in animals results in vitamin B6 deficiency and neurotoxicity. Fortunately, newer compounds devoid of such side effects, have opened exciting prospects. Widely used hypotensive agents, such as angiotensin converting enzyme (ACE) inhibitor and angiotensin II receptor antagonist, but not calcium blockers, prove more effective than AG in attenuating the production of AGEs. Unlike AG, they do not act as RCO trapping agents, but impact upon the production of RCO precursors by scavenging a variety of radicals and altering oxidative stress, a mechanism similar to that involved in the inhibitory action of nitric oxide on AGE formation. These results provide a new framework to assess families of compounds according to their mechanisms of action.
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PMID:Alterations of non-enzymatic biochemistry in uremia, diabetes, and atherosclerosis ("carbonyl stress"). 1250 15

Hyperglycaemia is considered to be the key causal factor in the development of diabetic complications. Poor glycemic control a significant changes of erythrocyte membrane fluidity, erythrocyte deformability and antioxidant status. Nonenzymatic glycation and glycoxidation with cascade of free radical reactions, oxidative and carbonyl stress may play an important role in the development diabetic micro- and macrovascular complications. The serum levels of specific and nonspecific advanced glycation end products (s-AGEs) have been found elevated in type 1 and type 2 diabetic patients. Levels of s-AGEs. may serve as useful biochemical marker for monitoring progression of diabetic complications and pathological processes. Accumulation of AGEs on tissue proteins increases with pathogenesis of diabetic complications and atherosclerosis. AGEs are believed to induce cellular oxidative stress through the interaction with specific cellular receptors. Carbonyl stress-induced tissue damage is caused by AGE precursors formed by hyperglycaemia, hyperlipidemia, nonenzymatic glycation, peroxidation of lipids and metabolis processes. The toxic effects of AGE precursors can not be directly antagonized by antioxidants. Only a small number of biological carbonyl scavengers like glutathione have been identified to date. For therapeutic intervention, nucleophilic compounds as aminoguanidine, pyridoxamine, OPB-9195, 2,3-diaminophenazone, carnosine and tenilsetam give promising results. These potential therapeutics have been proposed to trap AGE precursors. Studies in vitro showed that these AGE inhibitors have also the antioxidant and chelating activity. Angiotensin converting enzyme (ACE) and angiotensin II receptor antagonists also significantly attenuate AGE production. These drugs do not trap AGE precursors, but impact on the production of AGE precursors by chelating transition metals and inhibiting various oxidative steps in the process of glycoxidation, including the formation of free radicals. Finally, supplementation with antioxidants and antioxidant systems could be a complementary treatment in diabetic patients.
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PMID:[The role of nonenzymatic glycation and glyco-oxidation in the development of diabetic vascular complications]. 1282 98

Diabetic nephropathy has become the single largest cause of end-stage renal disease (ESRD) worldwide. Until recently, it was thought that once a patient developed overt proteinuria, diabetic nephropathy was irreversible and inevitably progressed to ESRD. However, the reversal of lesions caused by diabetic nephropathy (e.g., glomerular basement membrane thickening and mesangial matrix increase) has been demonstrated in a series of patients who underwent a pancreas transplantation 10 years prior to the reversal. Remission of nephrotic range proteinuria has also been reported in some patients with type 1 diabetes from the Collaborative Study Group during a median follow-up of 3 years of angiotensin-converting enzyme (ACE) inhibitor administration; no deterioration of renal function was observed in these patients. Remission and regression in nephropathy of type 1 diabetes patients have also been reported when blood pressure was controlled aggressively. Recent clinical trials have demonstrated that angiotensin II receptor blocker (ARB) preserved renal function and slowed the progression of nephropathy to ESRD in patients with type 2 diabetes. Since many patients with type 2 diabetes manifest with a metabolic syndrome, multifactorial intensive treatment is necessary; such treatment includes behavior modifications, dietary intervention, exercise, and smoking cessation. In this population, pharmacological therapy targeting hyperglycemia, hypertension (including ARB/ACE inhibitor), and hyperlipidemia in cases of type 2 diabetes is also necessary.
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PMID:Remission and regression of diabetic nephropathy. 1292 17


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