Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. There is an increased prevalence of hypertension, which is an important risk factor for progressive renal impairment, in patients with IgAN. Changes in sodium-lithium countertransport (Na/Li CT) kinetics, particularly high Vmax/Km, have been shown in familial essential hypertension. In this study a high Vmax/Km was observed in IgA probands with hypertension and/or progressive renal impairment. Mean blood pressure was higher in the first-degree relatives of patients with IgAN compared with relatives of normotensive IgAN probands. These hypertensive relatives had an increased Vmax/Vm ratio and a low Km of Na/Li CT. There is a strong correlation of Vmax/Vm (r = 0.82) between the IgA probands and their first degree relatives, suggesting strong familial factors contributing to this Na/Li CT kinetic parameter. An increased Vmax/Km ratio of Na/Li CT seems to be a better marker for familial hypertension than Km alone and may be useful in identifying those patients who are at a greater risk of developing hypertension.
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PMID:Abnormal sodium-lithium countertransport kinetics in immunoglobulin A nephropathy patients and the families: association with hypertension. 860 1

Increased platelet cytosolic free calcium concentration ([Ca2+]i) has been demonstrated in both human essential hypertension and spontaneous hypertension of the rat. The present study was designed to extend the investigation on platelet Ca2+ handling to two models of salt-dependent genetic hypertension (Sabra and Dahl rat strains). No major [Ca2+]i elevation was seen in salt hypertensive SBH Sabra or SS/Jr Dahl rats. This contrasts with the data obtained in Lyon hypertensive rats (a spontaneous form of genetic hypertension) in which basal platelet [Ca2+]i was clearly increased and correlated positively with diastolic blood pressure. In these two strains, basal platelet [Ca2+]i correlated with pulse pressure but not with diastolic pressure. The absence of a significant relationship between platelet [Ca2+]i and diastolic pressure in both Sabra and Dahl rats indicates that, at least in young rats with developing salt hypertension, platelet cytosolic calcium need not reflect calcium changes occurring in the vascular smooth muscle or resistance arterioles. In contrast to the high values seen in Lyon hypertensive rats, the [Ca2+]i rise induced by thrombin was unchanged in salt-sensitive SS/Jr Dahl rats and substantially reduced in hypertension-prone SBH rats (irrespective of salt intake). The initial rate of thrombin-induced Mn2+ entry through receptor-operated Ca2+ channels was similar in SBN and SBH as well as in SR/Jr and SS/Jr rats kept on a low-salt diet but was reduced by high salt intake in platelets of salt-resistant (SBN and SR/Jr) animals only. Since platelets of Lyon hypertensive rats are also characterized by greater initial rate of thrombin-induced Mn2+ entry, this parameter was always higher in rats with established hypertension compared to their respective normotensive controls. Our study demonstrated that alterations of platelet Ca2+ handling are different in salt-dependent than in spontaneous forms of genetic hypertension.
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PMID:Platelet calcium handling is different in rats with salt-dependent and spontaneous forms of genetic hypertension. 886 28

Ion transport abnormalities in essential hypertension are often associated with concomitant changes of lipid metabolism, but this information is missing in rats with genetic hypertension. We therefore studied the alterations of red cell Na+ and K+ transport and their relationship to blood pressure and plasma lipids (cholesterol and triglycerides) in Prague hereditary hypertriglyceridemic (HTG) rats, Lyon hypertensive (LH) rats, and HTG x Lewis F2 hybrids. In both hypertensive models and F2 hybrids, red cell Na+ content (Na+(i)) was positively related to plasma triglycerides but not to plasma cholesterol levels. Na+(i) elevation was more pronounced in HTG than in LH rats, probably due to higher plasma triglycerides in the former strain. The two hypertensive strains differed in bumetanide-sensitive Na+ transport, which was augmented in HTG rats with low plasma cholesterol but suppressed in LH rats characterized by high cholesterol levels. In the two genetic models, there was a positive association of blood pressure with Na+ leak, and this was also confirmed by the cosegregation of these parameters in F2 hybrids. We conclude that the enhancement of Na+ leak represents the major ion transport abnormality in rats with genetic hypertension. The alterations in plasma lipids are important determinants of abnormal red cell ion transport in hypertensive models studied. Although the detailed mechanism of their participation in ion transport regulation is still not completely understood, triglyceride-dependent changes in membrane microviscosity seem to be responsible for the modulation of particular ion transport pathways.
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PMID:Plasma triglycerides and red cell ion transport alterations in genetically hypertensive rats. 932 95

Peripheral glucose disposal (assessed with the euglycaemic-hyperinsulinaemic clamp technique), Na+-Li+ countertransport in erythrocytes and the cytosolic free Ca2+ concentration in platelets were determined in 36 men from families with essential hypertension in at least two close relatives and in 28 age- and weight-matched men from families without hypertension. All had diastolic blood pressure consistently below 90 mm Hg and a normal oral glucose tolerance test. The mean age of the study population as a whole was 37 years (range 24-46). Insulin sensitivity index values (glucose disposal/serum insulin concentration during the clamp) were lower in the familial hypertension group than in the control group, but the two groups did not differ in Na+-Li+-countertransport, or in the platelet cytosolic free Ca2+ concentration which was correlated to the waist: hip circumference ratio in both groups (r = 0.38 and r = 0.49, respectively). The present findings do not support the hypothesis that an increase in Na+-Li+ countertransport activity or the platelet cytosolic free Ca2+ concentration is a marker of insulin resistance in hypertension prone men.
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PMID:Insulin sensitivity, sodium-lithium countertransport and platelet free calcium concentrations in normotensive men with a family history of hypertension. 960 96

Gordon's syndrome (GS) is a salt-sensitive, hyperkalaemic, familial hypertension syndrome which may masquerade in milder forms as essential hypertension. The response of hyperakalaemia to dietary salt restriction and to mineralocorticoids is heterogeneous, suggesting genetic heterogeneity. In a recently published study using small pedigrees, possible linkage of GS to chromosomes 1 and 17 was described. Studying the largest pedigree so far reported with GS, and using fluorescent-labelled microsatellite markers, we sought evidence of linkage to chromosomes 1 and 17. In this family there was no segregation of GS with any of the markers for chromosome 1. On chromosome 17, however, evidence of linkage was found with a maximum multipoint LOD score of 2.4 (the maximum LOD possible from the pedigree) over markers D17S250 and D17S934. This represents strong evidence in this pedigree for a responsible gene mutation on the long arm of chromosome 17. Recent reports of linkage for essential hypertension and, especially, familial essential hypertension within the same area of chromosome 17 containing the D17S934 marker raise the possibility that the same gene may be responsible for familial essential hypertension and for Gordon's syndrome.
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PMID:Linkage of Gordon's syndrome to the long arm of chromosome 17 in a region recently linked to familial essential hypertension. 981 11

During the past decade, it has become evident that dopamine plays an important role in the regulation of renal function and blood pressure. Dopamine exerts its actions via a class of cell-surface receptors coupled to G-proteins that belong to the rhodopsin family. Dopamine receptors have been classified into two families based on pharmacologic and molecular cloning studies. In mammals, two D1-like receptors that have been cloned, the D1 and D5 receptors (known as D1A and D1B, respectively, in rodents), are linked to stimulation of adenylyl cyclase. Three D2-like receptors that have been cloned (D2, D3, and D4) are linked to inhibition of adenylyl cyclase and Ca2+ channels and stimulation of K+ channels. All the mammalian dopamine receptors, initially cloned from the brain, have been found to be expressed outside the central nervous system, in such sites as the adrenal gland, blood vessels, carotid body, intestines, heart, parathyroid gland, and the kidney and urinary tract. Dopamine receptor subtypes are differentially expressed along the nephron, where they regulate renal hemodynamics and electrolyte and water transport, as well as renin secretion. The ability of renal proximal tubules to produce dopamine and the presence of receptors in these tubules suggest that dopamine can act in an autocrine or paracrine fashion; this action becomes most evident during extracellular fluid volume expansion. This renal autocrine/paracrine function is lost in essential hypertension and in some animal models of genetic hypertension; disruption of the D1 or D3 receptor produces hypertension in mice. In humans with essential hypertension, renal dopamine production in response to sodium loading is often impaired and may contribute to the hypertension. The molecular basis for the dopaminergic dysfunction in hypertension is not known, but may involve an abnormal post-translational modification of the dopamine receptor.
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PMID:Renal dopamine receptors in health and hypertension. 983 70

Essential hypertension is known to be associated with a decrease in the lumen diameter and an increase in the wall thickness to lumen diameter ratio of the resistance vessels. Recently, it has been clarified that this alteration does not necessarily involve vascular growth, but could be due to a rearrangement of the same amount of material, a phenomenon now termed "eutrophic remodeling." These changes are found both in human essential hypertension and in animal models of genetic hypertension. Antihypertensive treatment with angiotensin-converting enzyme (ACE) inhibitors causes a dose-dependent regression of the media to lumen ratio in rats. Clinical studies have now confirmed these findings, showing that when previously untreated essential hypertensive patients are treated with the ACE inhibitor perindopril (PE), the abnormal structure of resistance vessels regresses toward normal values; in contrast, treatment with a beta-blocker does not affect the abnormal vascular structure. The available evidence thus indicates that ACE inhibitors are able to normalize the abnormal resistance vessel structure in essential hypertension, and suggest that this effect may not only be dependent on their ability to reduce blood pressure. This review summarizes these findings, and discusses the extent to which this is desirable.
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PMID:Effects of angiotensin-converting enzyme inhibition on vascular remodeling of resistance vessels in hypertensive patients. 986 66

Experimental models of genetic hypertension are used to develop paradigms to study human essential hypertension while removing some of the complexity inherent in the study of human subjects. Since 1991 several quantitative trait loci responsible for blood pressure regulation have been identified in various rat crosses. More recently, a series of interesting quantitative trait loci influencing cardiac hypertrophy, stroke, metabolic syndrome and renal damage has also been described. It is recognized that the identification of large chromosomal regions containing a quantitative trait locus is only a first step towards gene identification. The next step is the production of congenic strains and substrains to confirm the existence of the quantitative trait locus and to narrow down the chromosomal region of interest. Several congenic strains have already been produced, with further refinement of the methodology currently in progress. The ultimate goal is to achieve positional cloning of the causal gene, a task which has so far been elusive. There are several areas of cross-fertilization between experimental and human genetics of hypertension, with a successful transfer of two loci directly from rats to humans and with new pharmacogenetic approaches which may be utilized in both experimental and clinical settings.
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PMID:Genetics of experimental hypertension. 988 70

A genetic alteration in the adducin genes is associated with hypertension and up-regulation of the expression of renal Na, K-ATPase in Milan-hypertensive (MHS) rats, in which increased ouabain-like factor (OLF) levels are also observed. PST 2238, a new antihypertensive compound that antagonizes the pressor effect of ouabain in vivo and normalizes ouabain-dependent up-regulation of the renal Na-K pump, was evaluated for its ability to lower blood pressure and regulate renal Na,K-ATPase activity in MHS genetic hypertension. In this study, we show that PST 2238, given orally at very low doses (1 and 10 microg/kg for 5-6 weeks), reduced the development of hypertension in MHS rats and normalized the increased renal Na,K-ATPase activity and mRNA levels, whereas it did not affect either blood pressure or Na,K-ATPase in Milan-normotensive (MNS) rats. In addition, a similar antihypertensive effect was observed in adult MHS rats after a short-term treatment. In cultured rat renal cells with increased Na-K pump activity at Vmax due to overexpression of the hypertensive variant of adducin, 5 days of incubation with PST 2238 (10(-10-)-10(-9) M) lowered the pump rate to the level of normal wild-type cells, which in turn were not affected by the drug. In conclusion, PST 2238 is a very potent compound that in MHS rats reduces blood pressure and normalizes Na-K pump alterations caused by a genetic alteration of the cytoskeletal adducin. Because adducin gene mutations have been associated with human essential hypertension, it is suggested that PST 2238 may display greater antihypertensive activity in those patients carrying such a genetic alteration.
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PMID:PST 2238: A new antihypertensive compound that modulates Na,K-ATPase in genetic hypertension. 1002 44

The aim of this study was to investigate abnormalities in lymphocyte membrane sodium fluxes in patients with essential hypertension with and without familial history of hypertension and the influence of selected hypotensive drugs on these fluxes. 121 patients (pts) with positive family histories of primary hypertension (PFH) and 73 pts with negative family histories of primary hypertension (NFH) were examined. The total sodium efflux rate constant (wswc), ouabaine-sensitive (wswou) and furosemide-sensitive (wswf) were measured by the method of Heagerty et al. To examine the influence of selected hypotensive drugs on sodium fluxes wswc, wswou and wswf were measured before and after 7 days of treatment with hydrochlorothiazide (H) or propranolol (P). Wswou was decreased in 61% pts with PFH and in 19% pts with NFH, wswf was decreased in 38% pts with PFH and in 22% pts with NFH. Both, wswou and wswf, were decreased in 49% pts with PFH and only in 2.7% pts with NFH. Wswou and wswf rose significantly after 7 days of treatment with H or P only in pts with PFH and in pts with decreased wswou and wswf before treatment. These data suggest that abnormal lymphocytes membrane sodium transport often occurs in pts with PFH and has familial component. Changes in transport systems observed after 7 days treatment with H or P may contribute, at least in part, to its antihypertensive action in familial hypertension.
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PMID:[Studies of lymphocyte membrane transport of sodium in patients with essential hypertension]. 1036 94


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