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)

The tolerability and safety of candesartan cilexetil has been evaluated in over 5000 subjects enrolled into double-blind or open-label clinical studies. In double-blind clinical trials in patients with primary hypertension, candesartan cilexetil 2-16 mg once-daily was associated with a low incidence of adverse events and drug-related withdrawals, similar to placebo. The drug showed no evidence of dose-dependent adverse events and it was equally well tolerated by men and women and by elderly (> or =65 years) and younger (<65 years) patients alike. Candesartan cilexetil had no effect on blood glucose control or serum lipid profile in patients with type II diabetes. It was very well tolerated also when given in combination with hydrochlorothiazide or amlodipine and during long-term open-label therapy (up to 1 year). Candesartan cilexetil therefore possesses an excellent tolerability profile that extends to a wide variety of patients including the elderly and it does not aggravate co-existing risk factors such as hyperlipidaemia or glucose intolerance. It therefore appears to offer a better tolerated alternative to other commonly used antihypertensive agents.
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PMID:Candesartan cilexetil: safety and tolerability in healthy volunteers and patients with hypertension. 933 Oct 17

Current opinions on the relationships between erythrocyte sodium-lithium countertransport kinetics and primary hypertension, hyperlipidaemia and diabetic nephropathy are reviewed. Problems associated with the assay are analysed. Some possible mechanisms that could modify the kinetics of ion exchange are examined. The question of what catalyses sodium-lithium countertransport is discussed, but not answered. Some models are put forward showing how a study of sodium-lithium countertransport kinetics could further our understanding of important disease processes.
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PMID:Sodium-lithium countertransport: physiology and function. 953 10

In this review the usefulness of the measurement of erythrocyte Na+/Li+ countertransport (Na+/Li+ CT) activity is evaluated. In particular, the association between enhanced erythrocyte Na+/Li+ CT activity and essential hypertension, hyperlipidaemia and diabetic nephropathy is discussed. The conclusion of this review is that elevated erythrocyte Na+/Li+ CT activity is associated with essential hypertension and hyperlipidaemia. A relationship between Na+/Li+ CT activity and diabetic nephropathy is less evident. Despite a significant link of Na+/Li+ CT activity with hypertension and hyperlipidaemia, the diagnostic significance of Na+/Li+ CT activity is low. This is due to the large overlap between the results of control subjects and patients. The factors that contribute to this broad range are discussed in detail.
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PMID:Relevance of erythrocyte Na+/Li+ countertransport measurement in essential hypertension, hyperlipidaemia and diabetic nephropathy: a critical review. 965 6

In an open trial, the antihypertensive efficacy of felodipine and its effects on lipid metabolism were investigated in 117 Nordic patients with mild to moderate essential hypertension and hyperlipidaemia. In the intent-to-treat analysis (n = 106) a significant (p < 0.01) drop in the mean systolic and diastolic blood pressure values was observed between baseline and 24 weeks' treatment from 157/100 mmHg to 145/92 (supine) and from 155/103 to 145/96 mmHg (erect). No relevant differences were seen in the pulse rate. Median total cholesterol and triglycerides remained unchanged, whereas HDL-cholesterol increased significantly from 1.30 mmol/l to 1.33 mmol/l (p < 0.02); LDL- and VLDL-cholesterol, apolipoprotein A1 and apolipoprotein B remained unchanged during the 24-week treatment period. In the per protocol analysis (n = 76), blood pressure values changed significantly from 158/100 mmHg to 144/91 mmHg (supine) and from 157/104 mmHg to 143/95 mmHg (erect) (p < 0.01 for both). HDL-cholesterol increased significantly (p = 0.03), whereas LDL- and VLDL-cholesterol, total cholesterol and triglycerides, as well as the apolipoproteins, remained unchanged during the trial. Felodipine thus proved to possess positive effects on lipid parameters in hypertensive patients.
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PMID:Effects of felodipine ER, a dihydropyridine calcium antagonist, on blood pressure and serum lipids. 970 99

SYMPATHETIC NERVOUS SYSTEM AND HYPERTENSION: Biochemical, electrophysiological, pharmacological and haemodynamic findings support the existence of sympathetic nervous system activation in primary human hypertension. Analysis of regional sympathetic nervous system function, using both neurophysiological methods for measuring sympathetic nerve firing rates, and neurochemical techniques for quantifying regional noradrenaline spillover to plasma has demonstrated activation of the sympathetic nervous outflows to the heart, the kidneys, and skeletal muscle vasculature, particularly in younger patients. The initiating cause of this sympathetic nervous stimulation is unknown, but estimation of central nervous system noradrenaline turnover in hypertensive patients, using measurements of the washout of noradrenaline and its lipophilic metabolites into the internal jugular veins, indicates that activation of forebrain pressor noradrenergic nuclei is the probable underlying mechanism. CONSEQUENCES OF INCREASED SYMPATHETIC ACTIVITY: The sympathetic activation present in human hypertension no doubt contributes to the blood pressure elevation, and is a legitimate target for therapeutic intervention with imidazoline receptor-binding agents such as rilmenidine. In addition, the sympathetic nervous activation seems to have adverse consequences in hypertensive patients beyond initiating the blood pressure elevation. There is evidence that neural vasoconstriction has metabolic effects, in skeletal muscle impairing glucose delivery to muscle, causing insulin resistance and hyperinsulinaemia, and in liver retarding postprandial clearing of lipids, contributing to hyperlipidaemia. Cardiac sympathetic activation is demonstrably a cause of sudden death in heart failure patients; a comparable arrhythmogenic effect is probable in hypertension. A trophic effect of sympathetic activation on cardiovascular growth is also likely, contributing to the development of left ventricular hypertrophy. Rilmenidine, through its central nervous system actions, has been demonstrated to powerfully reduce sympathetic nervous activity in essential hypertension patients. INHIBITING THE SYMPATHETIC SYSTEM: As the clinical consequences of sympathetic nervous activation in essential hypertension appear to go beyond that of hypertension pathogenesis, extending to a causal influence in atherosclerosis development, cardiovascular hypertrophy and cardiac arrhythmias, it is possible that, of all antihypertensive drugs, those inhibiting the sympathetic nervous system might best reduce cardiovascular risk. This remains to be tested.
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PMID:High blood pressure management: potential benefits of I1 agents. 974 6

The human insulin-resistance syndromes, type 2 diabetes, obesity, combined hyperlipidaemia and essential hypertension, are complex disorders whose genetic basis is unknown. The spontaneously hypertensive rat (SHR) is insulin resistant and a model of these human syndromes. Quantitative trait loci (QTLs) for SHR defects in glucose and fatty acid metabolism, hypertriglyceridaemia and hypertension map to a single locus on rat chromosome 4. Here we combine use of cDNA microarrays, congenic mapping and radiation hybrid (RH) mapping to identify a defective SHR gene, Cd36 (also known as Fat, as it encodes fatty acid translocase), at the peak of linkage to these QTLs. SHR Cd36 cDNA contains multiple sequence variants, caused by unequal genomic recombination of a duplicated ancestral gene. The encoded protein product is undetectable in SHR adipocyte plasma membrane. Transgenic mice overexpressing Cd36 have reduced blood lipids. We conclude that Cd36 deficiency underlies insulin resistance, defective fatty acid metabolism and hypertriglyceridaemia in SHR and may be important in the pathogenesis of human insulin-resistance syndromes.
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PMID:Identification of Cd36 (Fat) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats. 991 87

Insulin resistance is a characteristic feature of different physiological states including puberty, pregnancy, elderly and is associated with numerous common medical disorders as obesity, diabetes mellitus type 2, hyperlipidaemia, essential hypertension. Tests used for estimation of insulin sensitivity in vivo can be divided into indirect tests measuring action of endogenous insulin, usually in response to a glucose stimulus, and direct tests measuring glucose metabolism in response to exogenous insulin. Indirect tests--oral glucose tolerance test, intravenous glucose tolerance test, minimal Bergmans method, continuous infusion of glucose with model assessment (CIGMA), hyperglycemic clamp and direct tests--intravenous insulin tolerance test, insulin suppression test, euglycemic clamp are described, and their advantages and disadvantages are discussed.
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PMID:[Tests for evaluating insulin sensitivity in vivo]. 1055 72

The possible relationship among ventricular arrhythmia(VA), blood lipid(BL) and left ventricular hypertrophy(LVH) were investigated in 92 patients with essential hypertension(EH). The results showed that the incidence of VA and complex VA and ventricular tachycardia(VT) were significantly higher in EH with LVH than those in EH with non-LVH. The incidence of VA and complex VA and VT were highest in hypertensive patients with LVH accompanied with hyperlipemia(HL), and VA seemed closely related to left heart structure and BL. The results suggest that LVH and HL are the two additive risk factors of occurrence of VA in patients with EH.
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PMID:[Relationship between ventricular arrhythmia and blood lipid in hypertensive patients with left ventricular hypertrophy]. 1068 60

Herein are described the development and certain properties of a new drug, pyrazinoylguanidine (PZG), intended for use as an adjunct in the treatment of hypertensive patients with type 2 diabetes, formerly called noninsulin dependent diabetes mellitus. PZG is an analog of the potassium sparing diuretic, amiloride. However, in diabetic patients, amiloride exacerbates hyperglycemia and hyperlipidemia, whereas PZG reduces them. In several studies, PZG not only reduced elevated blood pressure in subjects with essential hypertension, but also downregulated the glucose fatty acid cycle in hypertensive patients with type 2 diabetes. PZG was well tolerated in all patients, as well as in normal subjects whose blood pressures and glucose metabolism were unaffected by PZG. However, in normal subjects made hyperglycemic by giving them hydrochlorothiazide, coadministration of PZG returned blood glucose concentrations to normal. Mechanisms for these effects of PZG in human subjects were investigated in both normal Sprague-Dawley rats and rats made diabetic with streptozotocin (STZ). In isolated rat adipocytes stimulated with theophylline, PZG downregulated both lipolysis and cyclic AMP concentrations. PZG, as well as insulin, increased adipose cyclic nucleotide phosphodiesterase activity, whereas theophylline reduced it. In perfused rat liver, PZG decreased gluconeogenesis and cyclic AMP concentrations. Collectively, these studies illustrate how the side effects (toxicity) of certain drugs, such as the tendency of thiazide diuretics to cause hyperglycemia and hyperlipidemia, can be modulated and even reversed by slight changes in the chemical structure of the molecule, specifically by removal of the 3,5-diamino and 6-chloro substituents on the benzene ring of amiloride to produce PZG.
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PMID:Studies on pyrazinoylguanidine: a novel antihypertensive, hypoglycemic and lipolytic drug intended for adjunctive use in hypertensive patients with type 2 diabetes mellitus. 1078 66

The epsilon4 allele of apolipoprotein E (APOE) is reported to be a genetic risk factor of atherosclerosis through hyperlipidemia and late-onset Alzheimer's dementia. A recent report showed that a genetic variant (A -491T) in the promoter region of the APOE gene increases the risk of Alzheimer's disease. In the present study, we examined whether these APOE polymorphisms were genetically involved in essential hypertension. Japanese hypertensives (n=180) with a family history of hypertension and normotensive controls (n=195, sex and age matched with hypertensives) were recruited from the outpatients of Osaka University Hospital, and an informed consent to participate in the study was obtained from each person. APOE polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The frequencies of the A -491 allele in hypertensives and normotensives were 0.98 and 0.97, respectively, and the TT/-491 genotype was not found in either group. No significant differences between hypertensives and normotensives were observed in allele frequencies in either APOE polymorphism; however, the mean diastolic blood pressure in normotensive subjects with AA/-491 was significantly higher than in the subjects with AT/-491 (p < 0.01). These results suggest that the presence of the APOE promoter polymorphism is not a major risk factor for hypertension but that it does have some minor effect on basal blood pressure variation.
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PMID:Association of polymorphism in the promoter region of the apolipoprotein E gene with diastolic blood pressure in normotensive Japanese. 1082 Nov 38


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