In-vivo intracellular pH at rest and during exercise in patients with essential hypertension

Background Several studies in isolated cells have reported that intracellular pH (pHi) in individuals with essential hypertension may be relatively alkaline compared to normotensive individuals. Such an abnormality of pHi in hypertension would be consistent with enhanced sodium–hydrogen exchanger activity and may provide potential mechanisms by which hypertension and its complications could develop. Objectives To determine in-vivo intracellular pH of skeletal muscle at rest and during recovery from exercise-induced acidosis in hypertensive and normotensive subjects. Methods Using 31-phosphorus magnetic resonance spectroscopy, pHi of the dominant flexor digitorum superficialis was measured in 20 Caucasian subjects (14 male) with essential hypertension and 20 normotensive controls matched for gender, age, race and body mass index. Measurements were made at rest and during the exercise and recovery periods of a stepped incremental maximal exercise protocol. The rate of pHi recovery from exercise-induced acidosis was calculated by linear regression over the first 210 s of recovery from the pHi time plots of respective subjects. Results Mean resting pHi in the hypertensive (7.05 ± 0.04) and normotensive groups (7.06 ± 0.04) were not significantly different. There was a significant effect of gender on pHi: mean pHi was 7.07 ± 0.03 in males and 7.02 ± 0.03 in females, respectively (P < 0.0005). The mean intracellular pH achieved by exercise was 6.74 ± 0.31 in hypertensive individuals and not significantly different in normotensive individuals (6.68 ± 0.19;P = 0.4). The mean rate of pHi recovery in the hypertensives was 0.08 ± 0.03 pH units/min and not significantly different in normotensives (0.08 ± 0.02;P = 0.4). Conclusions These results contrast with previously documented abnormalities in the control of pHi in hypertension and demonstrate the absence of major in-vivo disturbances of pHi in skeletal muscle, both at rest and during recovery from exercise-induced acidosis, in essential hypertension. Therefore, it is possible that previously documented abnormalities of pHi and activity of the exchanger may be either specific to cell type or not present under in-vivo conditions.

[1]  G. Sagnella,et al.  Platelet sodium/hydrogen exchanger activity in normotensives and hypertensives. , 1999, Clinica chimica acta; international journal of clinical chemistry.

[2]  M. Thelen,et al.  Dynamic phosphorus-31 magnetic resonance spectroscopy of the quadriceps muscle: effects of age and sex on spectroscopic results. , 1999, Investigative radiology.

[3]  M. Burchardt,et al.  Na+/H+ exchange during an oral glucose challenge in patients with essential hypertension. , 1997, The Journal of endocrinology.

[4]  C. Juel.  Lactate-proton cotransport in skeletal muscle. , 1997, Physiological reviews.

[5]  W. Siffert,et al.  Sodium-proton exchange and primary hypertension. An update. , 1995, Hypertension.

[6]  D. Rosskopf,et al.  Role of sodium-hydrogen exchange in the proliferation of immortalised lymphoblasts from patients with essential hypertension and normotensive subjects. , 1995, Cardiovascular research.

[7]  J. Díez,et al.  Association of increased erythrocyte Na+/H+ exchanger with renal Na+ retention in patients with essential hypertension. , 1995, American journal of hypertension.

[8]  L. Revert,et al.  Intracellular calcium concentration and activation of the Na+/H+ exchanger in essential hypertension. , 1994, Kidney international.

[9]  G. Kemp,et al.  pH control in rat skeletal muscle during exercise, recovery from exercise, and acute respiratory acidosis , 1994, Magnetic resonance in medicine.

[10]  A. Coca,et al.  Erythrocyte Ion Fluxes in Essential Hypertensive Patients With Left Ventricular Hypertrophy , 1993, Circulation.

[11]  J. Díez,et al.  Erythrocyte anion exchanger activity and intracellular pH in essential hypertension. , 1993, Hypertension.

[12]  S. Wray,et al.  Changes of intracellular pH in rat mesenteric vascular smooth muscle with high‐K+ depolarization. , 1993, The Journal of physiology.

[13]  S. Wray,et al.  Extracellular pH signals affect rat vascular tone by rapid transduction into intracellular pH changes. , 1993, Journal of Physiology.

[14]  D. Rosskopf,et al.  Membrane sodium-proton exchange and primary hypertension. , 1993, Hypertension.

[15]  D. Rosskopf,et al.  Platelet Na+‐H+ exchanger activity in normotensive and hypertensive subjects: effect of enalapril therapy upon antiport activity , 1992, Journal of hypertension.

[16]  G. de Simone,et al.  Sodium-hydrogen exchange and cardiac hypertrophy in patients with primary hypertension. , 1991, Journal of hypertension. Supplement : official journal of the International Society of Hypertension.

[17]  L. Poston,et al.  Leucocyte intracellular pH and Na(+)-H+ exchange activity in essential hypertension: an in vitro study under physiological conditions. , 1991, Journal of hypertension.

[18]  J. Ritter,et al.  Sodium dependence of sodium-proton exchange in platelets from patients with essential hypertension. , 1991, Journal of human hypertension.

[19]  G. Radda,et al.  Evidence for abnormal Na+/H+ antiport activity detected by phosphorus nuclear magnetic resonance spectroscopy in exercising skeletal muscle of patients with essential hypertension. , 1990, Clinical science.

[20]  A. Aviv,et al.  Variations in the apparent pH set point for activation of platelet Na-H antiport. , 1990, Hypertension.

[21]  L. Ng,et al.  Kinetics of the human leucocyte Na(+)-H+ antiport in essential hypertension. , 1990, Journal of hypertension.

[22]  A. Simon,et al.  Platelet cytosolic proton and free calcium concentrations in essential hypertension. , 1989, Journal of hypertension.

[23]  L. Ng,et al.  Leucocyte intracellular pH and Na+/H+ antiport activity in human hypertension. , 1989, Journal of hypertension.

[24]  R. Deth,et al.  Effects of intracellular alkalinization on resting and agonist-induced vascular tone. , 1989, The American journal of physiology.

[25]  R. Alexander,et al.  Spontaneously hypertensive rat vascular smooth muscle cells in culture exhibit increased growth and Na+/H+ exchange. , 1989, The Journal of clinical investigation.

[26]  S Grinstein,et al.  Na+/H+ exchange and growth factor-induced cytosolic pH changes. Role in cellular proliferation. , 1989, Biochimica et biophysica acta.

[27]  P. Luyten,et al.  Accurate quantification of in vivo 31P NMR signals using the variable projection method and prior knowledge , 1988, Magnetic resonance in medicine.

[28]  J. Laragh,et al.  Intracellular pH in human and experimental hypertension. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[29]  I. Starkey,et al.  Recommendations on blood pressure measurement. , 1986, British medical journal.

[30]  R. Mahnensmith,et al.  The plasma membrane sodium-hydrogen exchanger and its role in physiological and pathophysiological processes. , 1985, Circulation research.

[31]  T R Brown,et al.  Phosphorus nuclear magnetic resonance of fast- and slow-twitch muscle. , 1985, The American journal of physiology.

[32]  R G Shulman,et al.  Cerebral metabolic studies in vivo by 31P NMR. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[33]  R. Thomas,et al.  An investigation of the ionic mechanism of intracellular pH regulation in mouse soleus muscle fibres , 1977, The Journal of physiology.

[34]  J. Pouysségur,et al.  Molecular physiology of vertebrate Na+/H+ exchangers. , 1997, Physiological reviews.

[35]  G. Radda,et al.  Proton efflux in human skeletal muscle during recovery from exercise , 1997, European Journal of Applied Physiology and Occupational Physiology.