Hypertensive sodium-proton exchanger phenotype persists in immortalized lymphoblasts from essential hypertensive patients. A cell culture model for human hypertension.

Rosskopf, Dieter; Frömter, Eberhard; Siffert, Winfried

doi:10.1172/jci116865

Cited by 122 publications

(94 citation statements)

References 25 publications

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“…Based on results that G protein-mediated signaling is enhanced in a subgroup of hypertensive patients, and that this phenotype is retained under cell culture conditions (Rosskopf et al 1993), a systematic sequencing strategy resulted in the discovery of a silent polymorphism in GNB3 (C825T), the gene for the Gβ3 subunit ). This gene is located on the short arm of chromosome 12, which has frequently been implicated as a hypertension locus, although current evidence suggests that the different loci do not completely overlap (Fig.…”

Section: Genetic Variants In the Gene For The Gα Subunit (Gnas) And Tmentioning

confidence: 99%

Genetics of arterial hypertension and hypotension

Rosskopf

Schürks

Rimmbach

et al. 2007

Naunyn-Schmied Arch Pharmacol

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Human hypertension affects affects more than 20% of the adult population in industrialized countries, and it is implicated in millions of deaths worldwide each year from stroke, heart failure and ischemic heart disease. Available evidence suggests a major genetic impact on blood pressure regulation. Studies in monogenic hypertension revealed that renal salt and volume regulation systems are predominantly involved in the genesis of these disorders. Mutations here affect the synthesis of mineralocorticoids, the function of the mineralocorticoid receptor, epithelial sodium channels and their regulation by a new class of kinases, termed WNK kinases. It has been learned from monogenic hypotension that almost all ion transporters involved in the renal uptake of Na + have a major impact on blood pressure regulation. For essential hypertension as a complex disease, many candidate genes have been analysed. These include components of the reninangiotensin-aldosterone system, adducin, β-adrenoceptors, G protein subunits, regulators of G protein signalling (RGS) proteins, Rho kinases and G protein receptor kinases. At present, the individual impact of common polymorphisms in these genes on the observed blood pressure variation, on risk for stroke and as predictors of antihypertensive responses remains small and clinically irrelevant. Nevertheless, these studies have greatly augmented our knowledge on the regulation of renal functions, cellular signal transduction and the integration of both. Together, this provides the basis for the identification of novel drug targets and, hopefully, innovative antihypertensive drugs.

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Section: Genetic Variants In the Gene For The Gα Subunit (Gnas) And Tmentioning

confidence: 99%

Genetics of arterial hypertension and hypotension

Rosskopf

Schürks

Rimmbach

et al. 2007

Naunyn-Schmied Arch Pharmacol

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“…Following various leads that suggested increased activity of the Na ϩ /H ϩ exchanger in various cells or tissues of hypertensive patients compared with findings in controls, Siffert and colleagues concentrated their effort on cultured lymphoblastoid cell lines obtained from normotensive controls and hypertensive patients (Rosskopf et al 1993). Nine cell lines, referred to as NT lines, were generated from normotensive males with a negative family history of hypertension and in whom low Na ϩ /H ϩ exchanger activity had been consistently recorded in both platelets and lymphocytes.…”

Section: G Protein 3 Subunitmentioning

confidence: 99%

Development of genetic hypotheses in essential hypertension

Lalouel

Rohrwasser

2001

J Hum Genet

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Essential hypertension illustrates the formidable task presented by the identification of genetic determinants of common disease. Making an initial genetic inference may prove difficult enough; the subsequent demonstration of functional significance at various levels of biological integration may be even more challenging. We review three instances in which an initial genetic inference has led to the development of testable hypotheses pursued at increasingly higher levels of biological organization. These include the adducin, the G protein 3 subunit, and the angiotensinogen hypotheses.

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“…12,13 Consequently, enhanced activity of the exchanger may contribute to cell growth and hypertrophy in cardiomyocytes. Interestingly, activity of the exchanger has been reported to be increased in isolated cells from some individuals with essential hypertension.…”

Section: Journal Of Human Hypertension (2001) 15 523-527mentioning

confidence: 99%

Platelet sodium-hydrogen exchanger activity and left ventricular mass

et al. 2001

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Introduction:The sodium-hydrogen exchanger (NHE) is integral to the processes that facilitate cell growth and may contribute to the development of left ventricular hypertrophy. The aim of this study was to examine the relationship between platelet sodium-hydrogen exchanger activity and left ventricular mass index (LVMI). Methods: Twenty male untreated Caucasians (mean age ؎ s.d.: 48 ؎ 13; body mass index: 29 ؎ 4 kg/m 2 ) with a wide range of blood pressures were studied (mean BP: 152 ؎ 22/93 ؎ 15 mm Hg; range: 115-190/61-117 mm Hg). Sodium-hydrogen exchanger activity was determined as the rate of sodium-dependent recovery of intracellular pH in isolated platelets loaded with BCECF and acidified to pH 6.25 using nigericin. LVMI was calculated from measurements made by M-mode echocardiography. Associations between continuous variables were examined using parametric tests. Results: The mean rate of pHi recovery was

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Hypertensive sodium-proton exchanger phenotype persists in immortalized lymphoblasts from essential hypertensive patients. A cell culture model for human hypertension.

Cited by 122 publications

References 25 publications

Genetics of arterial hypertension and hypotension

Genetics of arterial hypertension and hypotension

Development of genetic hypotheses in essential hypertension

Platelet sodium-hydrogen exchanger activity and left ventricular mass

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