Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the optimal discriminators for peripheral atherosclerosis, we studied retrospectively 49 male patients and 39 male controls between 40 and 60 years of age. In addition to hypertension, cigarette smoking, diabetes mellitus, and hyperuricemia, we determined the most common lipids, lipoproteins, and apolipoproteins. Highly significant differences of median values between patients and controls in decreasing order of magnitude were recorded for apo A-II/apo B, apo A-I/apo B, apo B, total cholesterol, and LDL-cholesterol. A retrospective classification of patients and controls under optimal conditions with one variable (apo A-I/apo B) yielded an error rate of 25%. We found that apolipoproteins were better discriminators for peripheral atherosclerosis than than were lipids or lipoprotein lipids. The application of a linear regression discriminant analysis including 29 variables greatly decreased the rate of error and increased the sensitivity and specificity of the classification. From 229 possible models, we used an economic selection strategy to sort out those which either gave the best segregation or were considered the most practicable. The optimal model with 14 variables gave an error rate of less than 5% for the group studied. Suboptimal models yielded error rates between 13% and 18%. We conclude that a mathematical treatment of laboratory data which includes lipid parameters in addition to apolipoprotein values can improve the classification of peripheral vascular atherosclerosis.
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PMID:Risk factors for peripheral atherosclerosis. Retrospective evaluation by stepwise discriminant analysis. 640 92

The effects of metoprolol, propranolol and hydrochlorothiazide on lipoprotein metabolism were studied in three different but comparable groups of middle-aged men with previously untreated hypertension (n=10, n=10, and n=11, respectively). All three treatments were associated with an increase in serum triglyceride and VLDL-cholesterol levels. Propranolol treatment was associated with consistent and significant decreases in HDL-cholesterol, apoA-I and A-II levels, whereas these changes during the other treatments were neither significant nor consistent. An increase in adipose tissue LPL-activity and a decrease in serum free fatty acids were seen in the propranolol treatment group. Significant changes were not observed in glucose tolerance or catecholamine excretion. The blood pressure reduction was similar in the three groups. The design of the present study was in some important respects different from that of others. This may help to explain why we found a difference between the two beta-blockers in our study.
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PMID:Effects of anti-hypertensive therapy on serum lipoproteins. Treatment with metoprolol, propranolol and hydrochlorothiazide. 661 45

The effect of the diuretic chlorthalidone (100 mg/day for 6 weeks) on serum lipoproteins was evaluated in 37 subjects. In 19 men with essential hypertension (aged 41 +/- 3 yr), 8 normal men (26 +/- 3 yr), or all of these men considered together, chlorthalidone significantly increased serum low density lipoprotein--cholesterol (LDL-C) by 20% (p less than 0.05 to less than 0.01). There was also a tendency for increased LDL-C in seven postmenopausal women (+/- 15%) but not in three premenopausal women with essential hypertension. High density lipoprotein--cholesterol was not significantly changed in hypertensive women or normal men and decreased slightly (p less than 0.05) in hypertensive men. Apolipoproteins A-I, A-II, and B were not changed significantly in women or men. Diuretic-induced lipoprotein alterations were not associated with altered plasma volume and unrelated to variations in serum potassium, glucose, insulin levels, blood pressure, and body weight. Short-term diuretic therapy with chlorthalidone may increase serum LDL-C in young or middle-aged men with normal or high blood pressure.
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PMID:Increased serum low-density lipoprotein cholesterol in men treated short-term with the diuretic chlorthalidone. 737 38

A-II exerts its activity on various target tissues by binding to its receptors. The discovery of local RASs and A-II receptors within various tissues has generated interest in the clinical usefulness of RAS inhibition by directly blocking the action of A-II at the receptor level. Different A-II receptor subtypes have been identified and subsequently termed AT1 and AT2. AT1-receptor subtypes are the predominant receptor subtypes existing in most organs and, by coupling to a transmembrane G protein, seem to be the main subtypes participating in the vasoactive responses of A-II. Saralasin, a peptide with specific A-II receptor-antagonistic activity, had limited practical long-term usefulness as a result of its short half-life, significant agonistic properties, and lack of oral bioavailability. The discovery of simple benzyl-substituted imidazoles, which possess weak but highly selective A-II receptor antagonistic properties, led to the development of losartan (DuP 753). Losartan is a potent, orally active, specific, competitive nonpeptide A-II receptor antagonist that appears to be an effective antihypertensive agent both in animal studies and in preliminary clinical trials. The therapeutic usefulness of losartan, however, is not limited to its antihypertensive effects. The potential benefits of A-II receptor antagonists include roles in postmyocardial infarction therapy, slowing A-II-induced cardiac hypertrophy, 154, 155 slowing the progression of heart failure, preventing postangioplasty restenosis, and in slowing the progression of renal disease. Furthermore, losartan, a selective A-II type 1 (AT1) receptor antagonist, has also been a valuable pharmacologic probe for studying the mechanism of A-II stimulation of its receptors. A-II receptor antagonism appears to be as effective as ACE inhibition in the treatment of hypertension and other pathologic processes that involve the RAS and may offer an alternative to those patients who cannot tolerate ACE inhibitors because of their side effects.
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PMID:Angiotensin II receptor antagonists: a new approach to blockade of the renin-angiotensin system. 817 70

To elucidate the physiology of active sodium transport (expressed as erythrocytic ouabian-sensitive sodium efflux rate constant = ERCos) in pregnancy and the influence of dietary sodium intake on that transport, active sodium transport was measured in 52 healthy pregnant women in week 16, 20, 24, 28, 32, 36 or week 38 of gestation. ERCos was not influenced by parity, dietary sodium intake or the development of pregnancy-induced hypertension. A statistical significant shift in ERCos was detected between week 24 and week 28 of gestation accompanied by a shift in intracellular sodium content. The meaning of this change in pregnancy remains unsolved, but an influence of ANP through A-II is suggested.
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PMID:Erythrocytic ouabain-sensitive sodium efflux rate constant in pregnancy. 833 35

More than 300 risk factors for coronary artery disease (CAD) have been described. There are important geographical and racial differences in both the prevalence of CAD and of potential risk factors. The purpose of this study was to determine the relationship between both the presence and extent of angiographically defined CAD in an Irish population and a spectrum of clinical risk factors, lipid profile and haemostatic variables. On univariate analysis, age, male gender, history of smoking, history of hypertension, total cholesterol, triglycerides, LDL, Cholesterol, the LDL:HDL ratio, apoprotein B-100 and the apoprotein B-100: A-II ratio were associated with the presence of CAD. However, in multivariate analysis only age, male gender, a history of smoking and the apoprotein B-100: A-II ratio remained significantly associated with the presence of CAD. These same risk factors and apoprotein B-100 were significantly associated with the extent of CAD on multivariate analysis. In addition, apoprotein B-100 levels appeared to be associated with disease extent. When all significant variables associated with the presence or extent of CAD were analysed together in a multivariate model, they only accounted for 28% of the variability in the distribution of CAD. Thus, advancing age, male gender, cigarette smoking and apoprotein B-100 appear to be important correlates of the presence and extent of CAD in this selected population. However, in individual patients most of the variability in the distribution of occlusive CAD remains unexplained.
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PMID:Lipid profile, haemostatic variables and angiographically-defined coronary artery disease: a cross-sectional study in an Irish population. 869 60

The objective of this study was to determine whether phenolic constituents present in red wine and grape juice modulate plasma lipid and lipoprotein concentrations in healthy human subjects. All subjects consumed in random order 375 ml of red or white wine per day or 500 ml of two different grape juices (high and low phenols) per day for periods of 4 weeks separated by 2-week periods of abstention while continuing normal activity and food intake, and their normal lives in a community setting. The subjects were 24 healthy males aged 26-45 years screened by clinical examination and laboratory tests to exclude hypertension, diabetes mellitus, hyperlipidemia and obesity, among others. Fasting blood was collected at the beginning and end of each beverage schedule for analysis of lipids and lipoproteins. Changes in plasma lipids and lipoproteins in response to each beverage were measured to determine whether these were altered by red wine and grape juice phenolics independently of the effects of ethanol. Both grape juices had virtually no effect. Red and white wines raised plasma HDL-cholesterol and apo A-I and apo A-II concentrations as well as the apo A-I:apo B ratio to a similar extent. Red wine also raised plasma triglyceride and total cholesterol concentrations. Neither wine affected plasma apo B or apo (a) concentrations. The favourable effects of wines in modulating plasma lipid and lipoprotein concentrations are probably due to their alcohol content and cannot be reproduced by grape juices.
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PMID:Wine: does the colour count? 881 66

Lp(a) levels are genetically determined and remain stable without major changes throughout lives. However, when an individual's Lp(a) levels are observed over a one-year period, they show spontaneous variation. The rate of intraindividual variation in Lp(a) was observed in 16 patients with hypertension, hyperlipidemia and/or glucose intolerance in a chronic stable state who regularly visited the hospital clinic once a month, at least 10 times during the year, and in whom a total of 42 blood and clinical chemistry tests including serum lipids, Lp(a) and apoproteins were performed. The rate of annual intraindividual variation of Lp(a) averaged out as 16.6%. The rate was 18.8% for isoform S4 (n = 10), 18.6% for S3 (n = 3), and although small in number of subjects, other isoforms showed minor variation rates. There was a significant negative correlation between the rate of variation (y%) and LP(a) level (xmg/dl) r = -0.605, p < 0.05, y = -0.461 x +29.8). Therefore, when Lp(a) was high, the rate of variation (SD%) was low. This was consistent with the finding that the rates of variation were low for isoforms S2, S3S4 and F, whose molecular weights were low, accompanied by high Lp(a) levels. On the other hand, when the relationship between Lp(a) level and the amount of variation (SD mg/dl) was examined, there was no correlation between the two, since the amounts of variation were almost constant at a level of 3.8 mg/dl, regardless of Lp(a) level. The annual variation of Lp(a) level was found to be related to three groups of factors based on comparison of the variations among WHO phenotypes of hyperlipidemias, univariate correlation analysis with the clinical parameters tested, and multivariate analysis: the first group of factors was related to structure and metabolism of very low-density lipoprotein such as triglycerides, phospholipids, apo C-II, C-III, E, A-II and uric acid; the second group was related to thrombosis centering on platelets; and the third group involved those in the acute phase reactions represented by 1 hr and 2 hr erythrocyte sedimentation rates.
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PMID:Intraindividual variations in lipoprotein (a) levels and factors related to these changes. 922 16

Several HDL binding proteins, quite disparate in structure, have recently been cloned and their role in HDL metabolism is currently being assessed. High density lipoprotein binding protein, HBP (vigilin), which lacks a transmembrane domain is responsive to cell cholesterol levels, but its physiological significance remains unknown. On the other hand much is known about SR-B1, a member of the class B scavenger receptors. The level of SR-B1 expression correlates with both the selective transfer of cholesteryl ester into cells and cholesterol efflux from cells, the transfers probably mediated after docking of HDL at the cell surface. SR-B1 exhibits broad ligand specificity and, in animal models, appears to be regulated by the action of pituitary hormones that stimulate steroidogenesis, suggesting an important role for steroid hormone production in supplying precursor cholesterol. Another candidate HDL receptor, HB2, one of a pair of liver HDL binding proteins, shows high sequence homology with adhesion molecules, particularly activated leukocyte-cell adhesion molecule (ALCAM). When HB2 is overexpressed in cells, HDL binding increases. After PMA-induced differentiation of monocytes into macrophages, HB2 mRNA is strikingly elevated, which correlates with increased binding of HDL, but is down-regulated by cholesterol loading of macrophages. The ligand specificity of the HDL receptors, confounded by nonspecific lipid interactions, remains controversial. Their affinity for apoA-I versus apoA-I/A-II-rich HDL particles has clinical implications; both specific sequences in apoA-I and amphipathic alpha-helices may determine binding events. Post-receptor-mediated signalling events may regulate cell functions which, although not primarily related to lipid transport, nevertheless protect against coronary artery disease. Growing evidence for the involvement of lipid-poor apoA-I as a mediator of such pathways is also discussed.
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PMID:High density lipoprotein receptors, binding proteins, and ligands. 992 47

Adhesion molecules on the endothelial cell membrane play an important role in the pathogenesis of atherosclerosis. Levels of soluble forms of cell adhesion molecules are reportedly elevated in patients with peripheral artery vessel disease and in patients with an atherosclerotic aorta. The present study investigated the association of serum levels of soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), and soluble P-selectin (sP-selectin) with coronary heart disease (CHD) and the extent of coronary atherosclerosis, and examined the influence of serum levels of lipids, lipoproteins and apolipoproteins (apo) in subjects with (n=52, M/F:43/9) and without (controls, n=40, M/F:25/15) angiographically proven coronary atherosclerosis. After controlling for age and gender, levels of sVCAM-1 (least squares mean +/- std error: 565+/-36 ng/ml vs 540+/-41 ng/ml, ns), sICAM-1 (261+/-17ng/ml vs 247+/-19ng/ml, ns), and sP-selectin (142+/-8ng/ml vs 149+/-10 ng/ml, ns) in patients with coronary atherosclerosis were not different from those in controls, as assessed by an analysis of covariance. After also adjusting for body mass index, hypertension, diabetes mellitus, and smoking by a multiple logistic function analysis, the association of sVCAM-1, sICAM-1, and sP-selectin with CHD was still not significant. Levels of sVCAM-1, sICAM-1, and sP-selectin were also not related to the extent of coronary atherosclerosis as judged by the number of stenosed vessels. However, inverse (p<0.05) relationships were observed between sVCAMs and serum levels of HDL3-cholesterol, apo A-II, and lipoprotein containing apo A-I and A-II, between sICAMs and levels of apo A-II and Lp A-I/A-II (Lp A-I/A-II), and between sP-selectin and lipoprotein containing only apo A-I. In conclusion, serum levels of soluble VCAM-1, ICAM-1, and P-selectin were not related to CHD or the extent of coronary atherosclerosis, but were inversely related to serum levels of high-density lipoprotein-related lipoproteins.
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PMID:Levels of soluble cell adhesion molecules in patients with angiographically defined coronary atherosclerosis. 1008 83


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