Na(+)-H+ antiporter phenotype, abundance, and phosphorylation of immortalized lymphoblasts from humans with hypertension.

Abstract

Previous studies have demonstrated an elevated Na(+)-H+ exchanger activity in various cell types from patients with essential hypertension. The phenotype of an increased maximal transport capacity is preserved in Epstein-Barr virus immortalized lymphoblasts from hypertensive patients. The mechanisms underlying this abnormality are unclear. In this study, we used lymphoblasts from hypertensive patients and normotensive control subjects with and without a family history of hypertension to determine (1) Na(+)-H+ exchanger activity using fluorometry with the pH indicator 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein, (2) Na(+)-H+ exchanger isoform 1 abundance with specific polyclonal antibodies, and (3) Na(+)-H+ exchanger phosphorylation by immunoprecipitation of the 32P-labeled transporter. Na(+)-H+ exchanger activity (in millimoles per liter per minute) measured when pHi was clamped at 6.0 was significantly higher in cells from hypertensive patients (18.8 +/- 0.6, P < .001) and those subjects with a family history of hypertension (16.4 +/- 0.6, P < .001) compared with normotensive control subjects (12.9 +/- 0.6). Exchanger abundance was identical in all three groups of subjects, indicating that increased activity in the hypertensive group was due to an elevated turnover number of the exchanger. Na(+)-H+ exchanger phosphorylation in quiescent cells was significantly elevated in cells from hypertensive patients (1.58 +/- 0.16, P < .001) compared with control subjects (1.00 +/- 0.07), and cells from normotensive subjects with a hypertensive family history showed intermediate values (1.23 +/- 0.14). Identical changes in Na(+)-H+ exchanger function and phosphorylation have been demonstrated in vascular smooth muscle cells from spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: L L Ng, F P Sweeney, M Siczkowski, J E Davies, P A Quinn, B Krolewski, A S Krolewski
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 25 Issue 5 Pg. 971-7 (May 1995) ISSN: 0194-911X [Print] United States
• PMID: 7737735 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Sodium-Hydrogen Exchangers

Topics

• Adult
• Cells, Cultured
• Female
• Humans
• Hydrogen-Ion Concentration
• Hypertension (metabolism)
• Lymphocytes (metabolism)
• Male
• Middle Aged
• Phenotype
• Phosphorylation
• Sodium-Hydrogen Exchangers (analysis, metabolism)