Kinetic properties of erythrocyte Na+-Li+ and Na+-H+ exchange in hypertensive patients

Semplicini, Andrea; Ceolotto, Giulio; Felice, Marcella; Reato, Stefania; Valle, Roberto; Gebbin, Annalisa; Fontebasso, Alessandra; Serena, Luca; Pessina, Achille C.

doi:10.1097/00004872-199512010-00009

Cited by 6 publications

(4 citation statements)

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“…3,17,22 The present study shows that PKC activation by PMA selectively normalises the low Hill's coefficient for H ϩ i activation in hypertensives. On the contrary, the effects of PKC activation upon the affinity constant (K m ) for intracellular protons (H ϩ i and V max of NHE are similar in normotensives and hypertensives.…”

Section: Discussionsupporting

confidence: 50%

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Effect of protein kinase C and insulin on Na+/H+ exchange in red blood cells of essential hypertensives

et al. 1999

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The kinetic properties of sodium-proton exchange are abnormal in human red blood cells of hypertensive patients and it has been demonstrated that the transport protein undergoes post-translational modifications able to affect its kinetic properties. Protein kinase C (PKC) activation decreases the affinity constant for intracellular protons while insulin increases the maximal rate of proton translocation. The present study therefore aimed to examine the relationships among PKC activity, fasting insulin levels and the kinetic behaviour of sodiumproton exchange in red blood cells from 20 normotensives and 36 hypertensives.In comparison with normotensive subjects, hypertensive patients had higher body mass index (26.2 ؎ 0.7 vs 23.6 ؎ 0.6 kg/m 2 , P Ͻ 0.05), higher fasting insulin levels (93.2 ؎ 10.8 vs 38.6 ؎ 2.9 pmol/L), increased maximal velocity of proton translocation (37.9 ؎ 2.7 vs 27.6 ؎ 1.9 mmol/L per cell ؋ h, P Ͻ 0.05), and reduced Hill's coefficient (1.6 ؎ 0.1 vs 2.0 ؎ 0.1, P Ͻ 0.01) of sodiumproton exchange.Basal PKC activity of the cytosol and membrane was similar in the study groups. However, after treatment

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Section: Discussionsupporting

confidence: 50%

“…17 From this population, we randomly selected 20 normo-insulinaemic normotensives and 36 hypertensives, to study the effects of PMA on NHE activation and on PKC activity of RBC membrane proteins. Their clinical characteristics are shown in Table 1.…”

Section: Study Populationmentioning

confidence: 99%

Effect of protein kinase C and insulin on Na+/H+ exchange in red blood cells of essential hypertensives

et al. 1999

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“…9 Heterotrimeric G proteins, on the other hand, are involved in the regulation of cellular transmembrane sodium exchange 10 that is found to be increased in insulinresistant subjects. 11,12 Finally, worldwide distribution 8 of the C825T dimorphism of GNB3 suggests that it might fulfill the criteria of a thrifty genotype. 13,14 Taken together, this evidence suggests a possible further association of the C825T dimorphism with insulin resistance, as recently suggested in a small study in patients with essential hypertension, 15 and atherosclerosis.…”

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confidence: 99%

Associations of a Human G Protein β3 Subunit Dimorphism With Insulin Resistance and Carotid Atherosclerosis

Wascher

Paulweber

Malaimare

et al. 2003

Stroke

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Background and Purpose-The C825T dimorphism of the gene encoding the human G protein ␤3 subunit (GNB3) is associated with hypertension and obesity. Although these findings suggest an association with insulin resistance and atherosclerosis, this hypothesis has yet been tested only partially. Methods-To investigate this hypothesis, the C825T dimorphism was determined in a population of 932 middle-aged white subjects of middle European (Austrian) origin. Insulin sensitivity was measured with the short insulin tolerance test; intima-media thickness of the carotid artery and morphological plaque burden were measured by ultrasound. Results-Insulin sensitivity was found to be significantly lower in carriers of the T allele (3.55Ϯ1.27 versus 3.92Ϯ1.30%/min, Pϭ0.012) in the group of male subjects with abdominal body fat distribution (waist-to-hip ratio Ͼ0.9). No effect was observed in women or men with a waist-to-hip ratio Ͻ0.9. Advanced carotid artery plaques were more frequent (odds ratio, 1.606; 95% confidence interval, 1.002 to 2.575; Pϭ0.04) in carriers of the T allele regardless of sex. No effect was observed with regard to carotid artery intima-media thickness. Conclusions-In summary, our results demonstrate that the GNB3 825T allele is associated with reduced insulin sensitivity in men with abdominal fat distribution and with more advanced carotid atherosclerosis in middle-aged white men and women.

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“…Hypertensives classified as "high LNE" according to red-cell LNE above the mean of the study group showed higher blood pressure and significantly different kinetic properties of the red cell Na + /H + exchange but similar V max . These data suggest that an increased LNE is more likely to reflect abnormal kinetic properties of Na + /H + exchange (reduced affinity for internal H+ and low Hill's number) than an increased number of transport units (182). These kinetic abnormalities may facilitate Li + movement across the membrane at physiological cell pH (7.2).…”

Section: Lne and Na + /H + Exchangementioning

confidence: 89%

The Li sup sup Na sup nbsp sup exchange in hypertension

Semplicini

Sartori²,

Ceolotto³

et al. 2003

Front Biosci

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The red cell membrane Li+/Na+exchange is a heteroexchange that operates in either direction across the cell membrane. It binds either Li+ or Na+ on one side of the membrane and it exchanges the transported species for either Li+ or Na+ on the opposite side in a stoichiometric ratio of 1:1. In the population, Li+/Na+exchange is unimodally distributed but skewed to the right. Such distribution results from superimposition of two normal distributions. Many laboratories have shown that red-cell Li+/Na+ exchange is increased in patients with essential hypertension, compared with normotensive controls. Among the various alterations of cell membrane cation transport reported in hypertension, the increase of red-cell Li+/Na+ exchange has been most widely investigated and confirmed. Moreover, increased Li+/Na+ exchange has been found in some clinical conditions related to hypertension, such as overweight and diabetes. Among diabetic patients, Li+/Na+ exchange is particularly high in patients with nephropathy, hypertension, and microalbuminuria, leading to the hypothesis that it can be considered a cellular marker of the risk of developing diabetic nephropathy. Furthermore, it is associated with severe and drug-resistant hypertension, insulin resistance, vascular and cardiac hypertrophy, hyperlipidemia, obesity, family history of hypertension, and of major cardiovascular accidents suggesting that high Li+/Na+ exchange could be a biochemical marker for increased cardiovascular risk. Regardless of its the pathophysiological significance, its measurement could be of clinical use as an intermediate phenotype of increased cardiovascular risk.

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Kinetic properties of erythrocyte Na+-Li+ and Na+-H+ exchange in hypertensive patients

Cited by 6 publications

References 0 publications

Effect of protein kinase C and insulin on Na+/H+ exchange in red blood cells of essential hypertensives

Effect of protein kinase C and insulin on Na+/H+ exchange in red blood cells of essential hypertensives

Associations of a Human G Protein β3 Subunit Dimorphism With Insulin Resistance and Carotid Atherosclerosis

The Li sup sup Na sup nbsp sup exchange in hypertension

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