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(Hypertension. 1995;25:971-977.)
© 1995 American Heart Association, Inc.
Articles |
Na+-H+ Antiporter Phenotype, Abundance, and Phosphorylation of Immortalized Lymphoblasts From Humans With Hypertension
From the Department of Medicine and Therapeutics, Leicester (UK) Royal Infirmary (L.L.G., F.P.S., M.S., J.E.D., P.A.Q.); Department of Cancer Biology, Harvard School of Public Health, Boston (B.K.); and the Joslin Diabetes Center, Boston, (A.S.K.), Mass.
Correspondence to Dr L.L. Ng, Department of Pharmacology, Clinical Sciences Bldg, Leicester Royal Infirmary, Leicester LE2 7LX, UK.
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. Our findings suggest that the elevated Na+-H+ exchanger activity in cells from human hypertensive patients is not associated with an increased exchanger abundance but may be related to increased exchanger phosphorylation.
Key Words: hypertension, essential • sodium-hydrogen exchanger • protons • phosphorylation
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