Elevation of red cell sodium-lithium countertransport in hyperlipidemias

Corrocher, Roberto; Steinmayr, Maria; Ruzzenente, Orazio; Brugnara, Carlo; Bertinato, Luciano; Mazzi, Maria Angela; Furri, C.; Bonfanti, F.; Sandre, G. De

doi:10.1016/0024-3205(85)90169-9

Cited by 74 publications

(32 citation statements)

References 32 publications

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“…Although the present study failed to detect any differences between the ethnic groups with respect to plasma HDL-cholesterol, this plasma lipoprotein tends to be elevated in black subjects. 33 When the negative correlation between the countertransporter and HDL-cholesterol reported by other investigators is taken into account 34,35 it may have bearing on the consistent reduction in V max observed in this study.…”

Section: Discussionsupporting

confidence: 68%

Kinetic characteristics of the erythrocyte sodium-lithium countertransporter in black normotensive subjects compared with three other ethnic groups

et al. 1998

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Sodium-lithium countertransport activity has been proposed as a marker for hypertension and is lower in black compared to Caucasian subjects both with and without vascular disease. The question arises of what is the primary kinetic locus of the altered behaviour of the countertransporter in black subjects and whether this is also seen in normotensive subjects from other non-Caucasian ethnic groups.We The clinical and laboratory characteristics of the subjects were similar in all four ethnic groups. Minor differences noted were: significantly higher mean height, weight and serum creatinine concentration (P Ͻ 0.001) and significantly lower plasma triglyceride concentration (P = 0.02) in the black compared to the other

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Section: Discussionsupporting

confidence: 68%

Kinetic characteristics of the erythrocyte sodium-lithium countertransporter in black normotensive subjects compared with three other ethnic groups

et al. 1998

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“…28 Hypertensive subjects with hyperlipidemia also had a significantly higher Li + -Na + countertransport than hypertensive subjects with normal plasma lipids. A weak association between hyperlipidemia and elevated countertransport also was reported by Hunt et al 29 and Duhm and Behr.…”

Section: Genetic Factors and Rbc LImentioning

confidence: 99%

The Li+-Na+ exchange and Na+-K+-Cl- cotransport systems in essential hypertension.

1987

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SUMMARY This review examines the physiological functions of the Li + -Na + exchanger and Na + -K+-CI" cotransport system in human red blood cells. Both transporters are family aggregated and determined mainly by genetic factors; they are present in kidney and vascular cells, where they are regulated by vasoactive substances. To assess the physiological function of these two transporters, we investigated their kinetic and equilibrium properties, and their modulation by vasoactive substances. Recent studies in red blood cells indicate that the Li + -Na + exchanger may be a mode of operation of the Na + -H + exchanger, which plays an important role in the regulation of cell pH, cell volume, and transtubular sodium transport. In vascular cells, Na + -H + exchanger is modulated by vasoconstrictors such as growth factors and angiotensin, while Na + -K + -Cl~ cotransport is modulated by vasodilators such as atrial natriuretic factor and bradykinin. Kinetic studies in red blood cells of hypertensive patients and their offspring indicate the presence of subsets with elevated V,,^ of Li + -Na + exchange or high K m for cell sodium for outward Na + -K + -Cl~ cotransport. The latter alteration is found most frequently in young blacks born of hypertensive parents, and it appears to be dependent on their level of sodium intake. The relationship between the alterations of the red blood cell sodium exchanger and Na + -K + -CI~ cotransport and risk factors for hypertension indicates that they can provide a tool to examine the interaction of genetic, hormonal, and environmental factors in human hypertension. 1. To define their physiological function and mechanism of regulation by studying their kinetic, equilibrium properties, and modes of operation. 2. To provide a tool for the study of genetic and environmental interactions in the etiology of human essentiaJ hypertension. 3. To assess whether alterations of these transporters in patients with essential hypertension may be due to a) differences in the number of transport sites; b) differences in the K m of the transport protein, which can alter their function; or c) differences in their modulation by vasoactive substances and/or growth factors.

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“…Observations that the V^ for Li + -Na + countertransport 1) is increased in some hyperlipidemic patients, 2 -5 2) correlates significantly with several plasma lipid components, 2 …”

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confidence: 99%

Effects of lovastatin treatment on red blood cell and platelet cation transport.

et al. 1991

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Hypercholesterolemia frequently accompanies hypertension, and it has been suggested that by affecting membrane lipid composition, hypercholesterolemia may cause or accentuate abnormalities in several red blood cell transports associated with hypertension. Such an effect might obfuscate the relation of membrane markers to hypertension and decrease their usefulness in genetic studies of the heritable basis of hypertension. To determine if changing plasma lipids affects membrane transport, we studied the effects of the cholesterol-lowering agent lovastatin on red blood cell lithium-sodium countertransport and sodium-potassium-chloride cotransport, red blood cell sodium and water content, and platelet amiloride-sensitive volume responsiveness to cytoplasmic acidification, an indirect measure of sodium-proton exchange that has been proposed as a new membrane marker for hypertension. In a 24 -week, placebo-controlled, double-blinded, randomized trial, lovastatin significantly lowered total and low density lipoprotein cholesterol and raised high density lipoprotein cholesterol. Red blood cell lithium-sodium countertransport and sodium-potassium-chloride cotransport were not significantly altered. Red blood cell sodium content decreased significantly in the lovastatintreated group, probably as a result of an increase in red blood cell sodium-potassium pump activity. Platelet amiloride-sensitive responses to cytoplasmic acidification were significantly depressed by lovastatin treatment, suggesting that lowering plasma cholesterol may suppress platelet sodium-proton exchange. It has been hypothesized that the hypeiiipidemias frequently observed in essential hypertensive patients may alter membrane lipid composition and affect membrane cation transport activities. Our observations on the effects of lovastatin treatment suggest that the abnormalities in lithium-sodium countertransport and sodium-potassiumchloride cotransport associated with human essential hypertension are unlikely to result from altered membrane cholesterol content or membrane cholesterol/phospholipid ratio. Altered membrane lipid composition may affect the sodium-potassium pump or sodium-proton antiport. olism cause or at least contribute to the increased Vnu,, for RBC Li + -Na + countertransport in hypertension.8 However, it is equally plausible that high total or low HDL cholesterol and hypertension are both features of a common underlying defect, such as that which may cause the syndrome characterized by Williams et al 9 as familial dyslipidemic hypertension. If an increased V,^ for RBC Li + -Na + countertransport is a marker for a genetic predisposition to familial dyslipidemic hypertension or related hypercholesterolemia syndromes, 10 then increased RBC Li + -Na + countertransport, hyperlipidemia, and hypertension could all be interrelated, but lipid levels per se would not necessarily contribute to elevated RBC Li + -Na + countertransport activity.We measured RBC Li + -Na + countertransport activity and plasma lipid levels in patients before and aft...

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Elevation of red cell sodium-lithium countertransport in hyperlipidemias

Cited by 74 publications

References 32 publications

Kinetic characteristics of the erythrocyte sodium-lithium countertransporter in black normotensive subjects compared with three other ethnic groups

Kinetic characteristics of the erythrocyte sodium-lithium countertransporter in black normotensive subjects compared with three other ethnic groups

The Li+-Na+ exchange and Na+-K+-Cl- cotransport systems in essential hypertension.

Effects of lovastatin treatment on red blood cell and platelet cation transport.

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