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)

The primary abnormalities that contribute to the pathogenesis of human essential hypertension are unknown. The known genetic contribution to this disorder suggests the possible use of genetic linkage analysis to test whether specific candidate genes contribute to the pathogenesis of either essential hypertension or intermediate phenotypes. Among such phenotypes, elevated erythrocyte Na(+)-Li+ countertransport (SLC) is the best known, supporting major gene inheritance by pedigree analysis. Striking similarities between SLC and Na(+)-H+ exchange suggest that mutations at the Na(+)-H+ antiporter gene locus (APNH) might result in elevated SLC and contribute to the subsequent pathogenesis of hypertension. We have tested these hypotheses by genetic linkage analysis, with APNH as a candidate gene. By determining genotypes at APNH and flanking loci in pedigrees that support major gene segregation of elevated SLC, we have excluded linkage of APNH and the major SLC locus with a LOD score of -5.91, an odds ratio of almost 1,000,000:1 against linkage. In the analysis of 93 hypertensive sibling pairs, we have further demonstrated that APNH explains none of the variance in SLC in hypertensive individuals (r2 = 6 x 10(-7), p greater than 0.99). Finally, we have directly tested for linkage of APNH to genes predisposing toward hypertension by linkage in hypertensive sibling pairs. Mean allele sharing at APNH is not greater than expected from random assortment in hypertensive siblings (0.92 versus 1.0, p greater than 0.80), and the upper 95% confidence limit of this value (1.04) indicates that mutations at APNH rarely if ever contribute to the pathogenesis of hypertension in this population.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Exclusion of the Na(+)-H+ antiporter as a candidate gene in human essential hypertension. 184 21

The rate of sodium-lithium countertransport (SLC flux) across red cell membranes has been reported to be elevated in hypertensive persons and their relatives as compared to normotensive individuals without family histories of hypertension. We have investigated the inheritance of this trait in 434 persons from 10 kindreds. Relatives show positive correlation of SLC flux values, but there is no spouse-spouse correlation. Pedigree analysis favors a model of polygenic inheritance over models of major-gene inheritance. Major-gene index statistics and offspring-between-parent statistics provide similar results. The proportion of total phenotypic variance that is attributable to polygenic differences between persons is estimated at 71%. The SLC flux values of hypertensive persons in this study population are lower than those reported from Boston, but are similar to those reported from Europe. We found a broad overlap of SLC flux values for hypertensive and normotensive persons. We conclude that SLC flux probably is not useful as a preclinical marker for essential hypertension.
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PMID:Genetic analysis of sodium-lithium countertransport in 10 hypertension-prone kindreds. 658 42

The erythrocyte Na+/Li(+)-countertransport activity was studied in patients with essential hypertension (n = 59), chronic glomerulonephritis (n = 30), chronic pyelonephritis (n = 26), renovascular hypertension (n = 35) and pheochromocytoma (n = 3). The erythrocyte Na+/Li(+)-countertransport (SLC) activity was on average higher (p < 0.02) in the patients with essential hypertension as compared to those with secondary hypertension, although a clear distinction between both groups was not possible. After surgical treatment of the patients with atherosclerotic renal artery stenosis, fibromuscular dysplasia or pheochromocytoma, no change in erythrocyte SLC activity was observed. However, blood pressure was significantly reduced.
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PMID:Red blood cell sodium-lithium countertransport in patients with essential and renal hypertension. 800 44

The correlation analyses were performed in 60 patients with essential hypertension (EHT) and 77 normotensives (NT) between RBC Na(+)-Li(+)-countertransport (SLC), Na(+)-K+ cotransport (SPT) and blood pressure, Quetelet index (QI), serum insulin, blood lipids, uric acid, blood glucose, etc. Results showed: (1) The SLC in EHT patients were higher, while SPT lower than NT group; (2) The difference between EHT and NT group was much prominent in SLC of male, while prominent in SPT of female; (3) There was no sex difference in SLC and SPT, and the SLC was correlated positively with QI3; (4) By multiple variants stepwise regression analysis, the SLC was shown to be associated positively with systolic and diastolic blood pressure; while the SPT inversely with systolic blood pressure. It suggests that SLC and SPT exert an independent effect on blood pressure.
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PMID:[RBC Na(+)-Li+ countertransport and Na(+)-K+ cotransport in patients with essential hypertension]. 819 29

An elevated activity of erythrocyte Na+/Li+ countertransport (SLC) is an intermediate phenotype of human essential hypertension, but cells other than erythrocytes have not been studied. Therefore, we have examined several transport modes of Na+/Li+ exchange in human skin fibroblasts. External Na+-stimulated Li+ efflux was 152 +/- 31 (SE) nmol x mg protein(-1) x min(-1) (n = 8). At intracellular pH 7.3, intracellular Na+-stimulated Li+ influx, intracellular Li+-stimulated Na+ influx, and external Li+-stimulated Na+ efflux were very similar, indicating the presence of a tightly coupled 1:1 SLC. This pathway was not affected by 5-(N,N-dimethyl)-amiloride and changes in the membrane potential, but phloretin and intracellular acidification (intracellular pH 6.8) were markedly inhibitory. Kinetic analyses of the external Na+ site also compared with SLC, although the internal site appeared to show a low affinity for Li+. We conclude that an SLC pathway similar to that in human erythrocytes is expressed in human skin fibroblasts.
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PMID:Modes of operation of an electroneutral Na+/Li+ countertransport in human skin fibroblasts. 914 64

Some patients with essential hypertension exhibit insulin resistance (IR) and several red blood cell (RBC) ion transport abnormalities. The aims of the study were to assess RBC ion transport acitivities under basal conditions, to test in vivo the effect of acute hyperinsulinemia, and to evaluate the relationship to IR in the offspring of hypertensive parents (n = 12; OHP) and healthy controls (n = 14; C). Activities of the Na+-K+ pump, Na+-K+ cotransport, Na+-Li+ countertransport (SLC), and Na+, Rb+, and Li+ leaks (passive membrane permeability) were measured before and after a hyperinsulinemic (75 microU/mL) euglycemic clamp (HIC) and compared to those found under isoinsulinemic isovolumic conditions in OHP and C. An insulin action was calculated as glucose disposal and insulin sensitivity index (M/I) after HIC. OHP were characterized by lower M/I (0.12+/-0.07 vs. 0.20+/-0.09 mg/kg/min/microU/mL; p < 0.05) and elevated SLC and Li+ and Rb+ leaks (p < 0.05) compared with C. Although acute hyperinsulinemia did not modify significantly any ion transport parameter studied, negative correlation was observed between insulin action and membrane cation leaks. Glucose disposal correlated with an Li+ leak in C (r = -0.736; p < 0.01) and all subjects (r = -0.424; p < 0.05) after HIC and in OHP with an Na+ leak (r = -0.727; p < 0.05) before HIC. In conclusion, OHP displayed higher insulin resistance, enhanced activity of SLC, and augmented Li+ and Rb+ leaks. Acute hyperinsulinemia did not modify any ion transport parameter studied, although negative correlation was observed between insulin action and membrane leaks.
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PMID:Erythrocyte membrane ion transport in offspring of hypertensive parents: effect of acute hyperinsulinemia and relation to insulin action. 1207 63

Human red blood cells possess a Na (+)H (+) antiporter in the plasma membrane that can exchange external Na(+) for intracellular H(+) when the intracellular pH falls below 7.0. The antiporter can also exchange Na(+) for Li(+) and that is named Na (+)Li (+) countertransport (SLC). This antiporter activity has been extensively investigated in essential hypertension and diabetes by clinical, epidemiologic, and genetic studies. Elevated values are found in patients with essential hypertension and diabetic nephropathy. In vitro studies in red cells of fasted individuals have demonstrated that physiologic doses of insulin increase the maximal transport rate and the K(m) for Na(+) of both Na (+)Li (+) and Na (+)H (+) exchanges. Ex vivo, SLC also exhibits elevated maximal activity and low affinity for Na(+) in insulin-resistant hypertensives. Patients with elevated antiporter activity manifest metabolic abnormalities (for example, high fasting insulin levels, hyperlipidemia, increased total body exchangeable Na(+), and renal and cardiac hypertrophy) that are part of the syndrome characterized by resistance to insulin-stimulated body glucose disposal. The coexistence of hypertension with insulin resistance and elevated SLC has suggested that a link between the metabolic and ion transport abnormalities may be mediated through chronic elevation of insulin levels. The association between circulating insulin concentrations and prevalence and severity of cardiovascular disease has been documented in many prospective population studies. Insulin modulation of this Na(+) antiporter might be an intermediate risk factor for cardiovascular disease that monitors chronic alterations of Na(+) homeostasis observed in hypertension and diabetes.
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PMID:Red cell sodium-lithium countertransport and cardiovascular risk factors in essential hypertension. 2123 45

Human NHA2, a newly discovered cation proton antiporter, is implicated in essential hypertension by gene linkage analysis. We show that NHA2 mediates phloretin-sensitive Na(+)-Li(+) counter-transport (SLC) activity, an established marker for hypertension. In contrast to bacteria and fungi where H(+) gradients drive uptake of metabolites, secondary transport at the plasma membrane of mammalian cells is coupled to the Na(+) electrochemical gradient. Our findings challenge this paradigm by showing coupling of NHA2 and V-type H(+)-ATPase at the plasma membrane of kidney-derived MDCK cells, resulting in a virtual Na(+) efflux pump. Thus, NHA2 functionally recapitulates an ancient shared evolutionary origin with bacterial NhaA. Although plasma membrane H(+) gradients have been observed in some specialized mammalian cells, the ubiquitous tissue distribution of NHA2 suggests that H(+)-coupled transport is more widespread. The coexistence of Na(+) and H(+)-driven chemiosmotic circuits has implications for salt and pH regulation in the kidney.
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PMID:Unconventional chemiosmotic coupling of NHA2, a mammalian Na+/H+ antiporter, to a plasma membrane H+ gradient. 2294 42