Intracellular Na<sup>+</sup>as a Genetic Marker of Essential Hypertension

Losse, H; Zidek, Walter; Zumkley, H; Wessels, F; Vetter, Hans

doi:10.3109/10641968109033689

Cited by 46 publications

(14 citation statements)

References 6 publications

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“…Intracellular Na+ concentration is elevated in red blood cells of individuals with essential hypertension as compared to controls (Losse et al, 1981). Although this observation was made in 1960, it went largely unappreciated until recently, when a flurry of activity centered on the usefulness of this trait as a marker in asymptomatic hypertension-i.e, as a predictor of subsequent hypertension, and as a possible key to a causal mechanism (Canessa et al, 1980;Garay et al, 1980Garay et al, , 1981Meyer and Garay, 1981;Losse et al, 1981).…”

Section: Blood Pressure and Psychological Variablesmentioning

confidence: 99%

Genetic and familial factors in essential hypertension and related traits

Siervogel

1983

American J Phys Anthropol

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The health significance of essential hypertension (high blood pressure of undefined origin) is well established. It is a major factor contributing to coronary heart disease, stroke, and kidney failure. It directly affects about one in five Americans. Factors which are known to be associated with blood pressure include: body composition as it relates to overall mass and fat mass; physiological variables involving the sympathetic and parasympathetic nervous systems; biochemical variables such as renin, aldosterone, kallikrein, lipids, and lipoproteins, etc.; environmental variables such as sodium intake, heavy metals, and noise; and psychological variables involving personality type and mental stress.There is a definite, well-established genetic involvement in hypertension, but specific genetic mechanisms remain a mystery. Familial aggregation occurs for many of the associated traits listed above. For some, specific polymorphic major genes have been identified, but for others genetic factors are unidentified. Essential hypertension is undoubtedly a heterogeneous group of diseases with the common end result of elevated blood pressure. Because of its health significance, there is considerable interest in identifying genetic mechanisms resulting in essential hypertension. One area that currently shows some potential for the identification of a specific genetic mechanism is related to the transmembrane transport of sodium and potassium cations.A genetic component has long been suspected in essential hypertension, but a clear and definitive genetic mechanism has yet to be identified. Since there are many variables that can affect blood pressure, this review of the genetics of essential hypertension necessarily involves a discussion of related traits. Before focusing on the genetic and familial aspects of hypertension a description of the normal course of human blood pressure is presented and some of the traits related to it are discussed. NATURAL HISTORY OF BLOOD PRESSUREUntil recently, reports describing blood pressure patterns during the neonatal period were relatively few, largely because of the difficulty of accurately measuring blood pressure in infants by noninvasive techniques. The ultrasonic technique utilizing the Doppler effect greatly facilitated noninvasive systolic blood pressure determination in infants (McLaughlin et al., 1971). Accurate automatic methods are currently available using the oscillometric principal coupled with a microcomputer and a standard limb blood presure cuff (Friesen and Lichtor, 1981). Even in adults newer methods are being developed (Wolthuis et al., 1981).© 1983 Alan R. Liss, Inc. [Vol.26,1983 Systolic blood pressure tends to increase sharply during the first two weeks of life from a mean of 70 mmHg at 2 days to 84 mmHg at 2 weeks. It continues to increase at a slightly slower rate over the next 4 weeks to a mean of about 93 mmHg at 6 weeks (Earley et aI., 1980); from 6 weeks to 1 year af age there is little change in systolic pressure (deSwiet et aI., 1975(deSwiet et ...

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Section: Blood Pressure and Psychological Variablesmentioning

confidence: 99%

Genetic and familial factors in essential hypertension and related traits

Siervogel

1983

American J Phys Anthropol

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“…8 ' l3 Elevated values have been reported in hypertensive subjects and in their normotensive first-degree relatives for Na + ,K + -adenosine triphosphatase (ATPase) pump, 14 intralymphocytic sodium, 15 and intraerythrocytic sodium. 16 These reported studies suggest that cation measurements are associated with hypertension and may provide biochemical manifestations of a developing familial syndrome before blood pressure abnormalities are manifest. Further family and pedigree studies are being carried out in several locations to see if shared family environment, major genes, or polygenes have an effect on cation tests.…”

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confidence: 97%

“…1 " 16 Sodium-lithium countertransport has been studied and reported most widely. Higher mean values for this test have been generally observed in persons with essential hypertension and in their normotensive first-degree relatives.…”

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confidence: 99%

Genetic studies of cation tests and hypertension.

et al. 1987

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SUMMARY Several tests of cation concentration and transport are being studied among members of large Utah pedigrees as part of a study of the genetic and environmental determinants of essential hypertension. Corrected urinary sodium excretion and plasma sodium concentration correlated well in spouses and siblings (r = 0.21-0.54, p< 0.001), suggesting the effects of shared family environment (e.g., sodium intake). Intraerythrocytic sodium concentration and sodium-lithium countertransport showed no significant correlation in spouses and very significant correlations between siblings and between parents and offspring (r = 0.34-0.58, p<0.001), suggesting mostly genetic determination. Using maximum likelihood tests of different genetic models, both sodium-lithium countertransport and intraerythrocytic sodium showed predominantly polygenic determination (H 2 = 70%) and some possible major gene determinants (H 2 = 18-25%) for a total heritability of 89 to 95% for these characteristics. These data suggest both genes and shared family environment contribute to the familiality of cation tests. They also illustrate the need and utility of quantitative methods for objective analysis of pedigree data.

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“…Differences in intraerythrocytic 10 and intralymphocytic 20 Na have previously been demonstrated between EH and N" subjects. 21 In our current study, there was a significant difference in [Na], between EH and N" groups, but the overlap of values was considerable.…”

Section: Content Of Sodium Red Blood Cellsmentioning

confidence: 80%

“…Therefore, we have used the pCMBS (parachloromercuribenzenesulfonate) loading technique of Dagher and Garay 3 to study the RBC cotransport activity of a large population of adult black men. We also measured the RBC Na content, because previous studies 10 in white populations have shown elevated levels among patients with EH.…”

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confidence: 99%

Red cell cotransport activity and sodium content in black men. Relationship to essential hypertension.

Ringel¹,

Hamlyn²,

Schaeffer³

et al. 1984

Hypertension

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SUMMARY Furosemide-sensitive sodium and potassium cotransport and intracellular sodium content ([Na],) were measured in erythrocytes (red blood cells, RBCs) from a population of 90 adult black men with and without essential hypertension (EH). The mean values for sodium cotransport activity, expressed as furosemide-sensitive Na efflux (mmol/liter RBC/hr), were not significantly different among the EH patients and two control groups, normotensive subjects with a positive history (N + ) and those with a negative family history (N-) for hypertensive disease (EH: 154 ± 123, n = 53; N+:167 ± 93, n = 12; and N~: 207 ± 142, n = 20; all values are means ± SD). The mean [Na], 9.66 ± 3.02 mmol/liter RBC (n = 56) for the EH group was greater than the mean value for the N~ control group (7.96 ± 1.97, n = 20; p < 0.05). The N+ group also displayed a higher mean [Na], (10.38 ± 3.18, n = 12; N + vsN~ p< 0.01). Although there was substantial overlapping of [Na], values between the groups and no clear dividing line, the distribution curve of the [Na], values in EH was skewed toward higher concentrations than in N~. Nevertheless, we must conclude that erythrocyte cotransport and [Na], are not clinically useful in the identification of EH in black men. (Hypertension 6: 724-730, 1984) KEY WORDS • essential hypertension • sodium • erythrocyte E SSENTIAL hypertension (EH) is a major public health problem in industrialized countries. It is generally accepted that heredity plays an important role in the etiology of EH although the extent of involvement is still unresolved.1 Studies 2 in strains of rats that become hypertensive on high salt diets (Dahl salt-sensitive rats) have demonstrated a genetically transmitted defect of renal sodium (Na) excretion, the hypertensive effects of which are humorally mediated. The cellular factors responsible for the Na excretion deficiency have not been identified, but the involvement of renal cellular cation transport From the Division of Pediatric Cardiology

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Intracellular Na⁺as a Genetic Marker of Essential Hypertension

Cited by 46 publications

References 6 publications

Genetic and familial factors in essential hypertension and related traits

Genetic and familial factors in essential hypertension and related traits

Genetic studies of cation tests and hypertension.

Red cell cotransport activity and sodium content in black men. Relationship to essential hypertension.

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Intracellular Na+as a Genetic Marker of Essential Hypertension

Cited by 46 publications

References 6 publications

Genetic and familial factors in essential hypertension and related traits

Genetic and familial factors in essential hypertension and related traits

Genetic studies of cation tests and hypertension.

Red cell cotransport activity and sodium content in black men. Relationship to essential hypertension.

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Intracellular Na⁺as a Genetic Marker of Essential Hypertension