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

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SUMMARY Alterations of cellular function of Na+ ,K + -edenosine triphosphatase (ATPase; Na + -K + pomp) have been implicated in the pathophyslology of essential hypertension. Therefore, this aspect of red blood cell (RBC) Na metabolism was studied in black men with newly diagnosed, untreated essential hypertension (NEH) and a normotensive control group. RBC Na content, Na + -K + pump number (ouabain binding sites), and pomp activity were measured. No statistically significant differences were found between the two groups for any of these three parameters. However, a group of previously treated essential hypertensive subjects (PEH) who had been withdrawn from therapy in the preceding 6 weeks were also studied. This group differed significantly from the NEH subjects in regard to all RBC Na + -K + pump parameters. Their RBC Na content (10.27 ± 3.23 vs 7.77 ± 2.52 mmol Na/L RBC; p = 0.006) was higher, and their Na + -K + pump activity (166 ± 50 vs 221 ± 87 nmol inorganic phosphate/mg membrane protein/hr; p = 0.03) and Na + -K + pump number (213 ± 40 vs 284 ± 85 binding sites/RBC; p = 0.001) were lower compared with those in NEH subjects. Although the PEH subjects were older and somewhat less hypertensive than their NEH counterparts, these factors were not found to influence the Na + -K + pump parameters. These results indicate that chronic diuretic therapy of patients with essential hypertension is associated with a reduced number of RBC Na + -K + pumps, Since RBCs are not considered target cells for diuretics, the effects of these drugs on RBC electrolyte metabolism may occur at the time of erythropoiesis by the production of RBCs with fewer Na + -K + pumps. Furthermore, the finding of elevated RBC Na content in PEH subjects acutely withdrawn from diuretic therapy is compatible with the renewed production of an endogenous natriuretic hormone that functions as a Na + -K + pump inhibitor.

Section: Discussionmentioning

confidence: 99%

Red blood cell Na+,K+-ATPase in men with newly diagnosed or previously treated essential hypertension.

Ringel¹,

Hamlyn²,

Hamilton³

et al. 1987

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“…However, outward K cotransport did not differ between study groups. Ringel et al 23 also found no difference in RBC Na + -K + outward cotransport between normotensive and hypertensive black men, noting that cotransport was not different between normotensive black men with and without a family history of hypertension. We previously reported lower mean levels of RBC outward Na + -K + cotransport in black normotensive and hypertensive subjects as compared with whites and no effect of family history of hypertension on cotransport function in blacks.…”

Section: Intracellular Cation Concentrationmentioning

confidence: 94%

“…A high K m value for Naj activation of outward Na + -K + cotransport has been reported in young blacks with salt-sensitive hypertension. 23 Thus, a major difference in RBC cotransport between blacks and whites appears to be a reduced affinity of Naj for its internal cotransport binding site in black subjects. In some blacks the high K 05 was accompanied by low V,^ values, but in others Vr eached normal levels.…”

Section: Intracellular Cation Concentrationmentioning

confidence: 99%

Kinetic analysis of erythrocyte Na+-K+ pump and cotransport in essential hypertension.

Tuck¹,

Corry²,

Maxwell³

et al. 1987

SUMMARY Alterations in red blood cell (RBC) Na + -K + pump and Na + -K + cotransport have been described in essential hypertension. We evaluated Na + -K + pump and cotransport in 30 hypertensive and 26 normotensive subjects subdivided by race and family history of hypertension using an improved method to examine the kinetics of Na and K effluxes. RBCs were Na-loaded by the nystatin method to five different levels of internal Na with pump determined as ouabain-sensitive Na efflux and cotransport as furosemide-sensitive Na and K efflux. Two kinetic parameters were determined for both transport systems: the apparent affinity for Na (K 0 . s ) and the velocity of efflux at saturating internal Na concentration (V max ). Mean intracellular Na content in fresh RBCs (mniol/L cells) was higher in black hypertensive (12.6 ± 1.8 mmol/L cells) and normotensive subjects (10.9 ± 1.2 mmol/L cells) than in white hypertensive (8.7 ± 1.0 mmol/L cells) or normotensive subjects (8.5 ± 0.8 mmol/L cells). The V mai and K 0 .s for pump were not significantly different between study groups. The V max for cotransport was elevated in white hypertensive compared with normotensive subjects, but the K 0 .s values were similar. Black normotensive and hypertensive subjects displayed a lower V max and increased K 0 _ s for cotransport compared with the white groups. A family history of hypertension had no influence on cotransport kinetics in blacks but did predict white normotensive and hypertensive subjects with low cotransport. The reduction in intracellular Na affinity for cotransport in black subjects may explain their higher intracellular Na in fresh RBCs. The wide range of cotransport V max with normal K os in white hypertensive subjects suggests an abnormality in cotransport activity in this population that differs from that in blacks. This study also demonstrates that the RBC pump, as evaluated by cation flux methodology, functions normally over a wide range of intracellular Na in the hypertensive population. (Hypertension 10: 204-211, 1987)

“…Indeed, these authors were unable to detect any abnormality in the erythrocyte Na + contents of American hypertensive patients. 2 In conclusion, the extensive investigation of Na + transport systems in erythrocytes from essential hypertensive patients supports the idea that none of the red blood cell abnormalities (and even less the "increased red cell Na + content") is a common denominator of primary hypertension. Conversely, it appears that "essential hypertension" is a common denominator of very different diseases at the molecular level.…”

mentioning

confidence: 61%

Red blood cell Na+ content is poorly related to essential hypertension and to membrane Na+ transport abnormalities.

Garay¹

1990

Letters to the Editor will be published, if suitable, as space permits. They should not exceed 1,000 words (typed double-spaced) in length and may be subject to editing or abridgment.Red Blood Cell Na + Content is Poorly Related to Essential Hypertension and to Membrane Na + Transport AbnormalitiesTo the Editor:Cooper et al 1 have recently published that "An increase in the content of sodium (in red cells from essential hypertensive patients) has been the most reproducible finding and is supported by the larger set of data." This is not only wrong, but the opposite is true (i.e., red blood cell Na + content has been found normal in most, if not all, essential hypertensive patients studied) (see References 2-4). Indeed, Wessels and Zumkley 5 needed to increase the number of (untreated) hypertensive patients studied to 295 to obtain statistically significant results (12% increase in mean Na + content with a large overlap between hypertensive and normotensive subjects). The small relevance of sodium content is further illustrated by a recent study of 127 French urban men where blood pressure was not correlated with erythrocyte Na + content. 6 Cell Na + content is the final resultant of the activity of all membrane Na + transport systems. In human red blood cells, Na + content simply depends on the balance between Na + entry by passive permeability (Na + leak) and active Na + extrusion by the Na + -K + pump. Interestingly, most red blood cell Na + transport abnormalities in essential hypertensive patients are unable to modify erythrocyte Na + content because they affect vestigial transport systems or are compensated by the pump (Table 1). Table 1 shows that the most frequent red blood cell abnormalities affect vestigial transport systems (i.e., the one-to-one Na + -Na + exchange [physiological counterpart of the Na + -LJ + countertransport], an Na + carrier unable to perform net Na + fluxes, and the Na + -K + -Cl~ cotransport system, a transport system catalyzing small Na + fluxes [which are near to equilibrium under physiological conditions]).Regarding the Na + -K + pump, the decreased affinity for internal sodium [R(-) abnormality] is compensated by an increased maximal pump rate [V( + ) abnormality], ensuring normal Na + efflux under physiological conditions. Another pump abnormality (i.e., decreased maximal pump rate [V(-)] in Table 1) was found in red blood cells from adult spontaneously hypertensive rats and rats with reduced renal mass (due to the presence of circulating endogenous "digitalislike" factors, see . This results in a decreased pump activity (under physiological conditions) and increased erythrocyte Na + content. The work of Rygielski et al 16 suggests that a very small fraction of essential hypertensive patients may have such "decreased pump/increased cell Na + content."In addition to the pump, the second transport pathway controlling red blood cell Na + content is the membrane Na + leak. However, 50-70% of the hypertensive patients with increased membrane Na + leak have normal red blood cell Na...