Bueno, J. (José)

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  • Enhanced Na(+)-H+ exchanger activity and NHE-1 mRNA expression in lymphocytes from patients with essential hypertension
    (American heart association, 1995) Arrazola, A. (Arantxa); Fortuño, A. (Ana); Diez-Martinez, J. (Javier); Tisaire, J. (Javier); Garciandia, A. (Ana); Lopez, R. (Rafael); Bueno, J. (José)
    It has been demonstrated that the activity of the sodium-proton exchanger (NHE-1 isoform) is increased in lymphocytes and other blood cells from patients with essential hypertension. In the present study, we investigated whether an increased level of NHE-1-specific mRNA in lymphocytes from patients with essential hypertension would explain the enhanced transport activity. Twenty-two hypertensive patients and 21 normotensive subjects were studied. Basal cytosolic pH was measured by the pH-sensitive fluorescent probe 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Maximal sodium-proton exchange activity was determined by acidifying cell pH and measuring the initial rate of the net sodium-dependent proton efflux driven by an outward proton gradient. The transcript level of NHE-1 was measured by reverse transcription-polymerase chain reaction in comparison with a constitutively expressed reference gene (beta-actin). Intracellular pH was lower in hypertensive patients than normotensive subjects (7.34 +/- 0.01 versus 7.39 +/- 0.01, mean +/- SEM, P < .001). The maximal activity of the sodium-proton exchanger was higher in hypertensive patients than in normotensive subjects (1262 +/- 100 versus 881 +/- 56 mmol/L cells per hour, P < .01). NHE-1 mRNA was increased in hypertensive patients compared with normotensive subjects (ratio of NHE-1 mRNA to beta-actin mRNA, 0.16 +/- 0.01 versus 0.12 +/- 0.02, P < .05). These data suggest that the increased sodium-proton exchange activity in essential hypertension may be related to the de novo synthesis of exchanger protein.
  • Angiotensin converting enzyme inhibition corrects Na+/H+ exchanger overactivity in essential hypertension
    (Nature publishing group, 1997) Fortuño, A. (Ana); Diez-Martinez, J. (Javier); Tisaire, J. (Javier); Lopez, R. (Rafael); Bueno, J. (José)
    In this study, we investigated whether antihypertensive treatment with the angiotensin converting enzyme inhibitor quinapril modifies Na+/H+ exchanger activity or NHE-1 (isoform of the exchanger) mRNA expression in lymphocytes from patients with essential hypertension. Thirty-three hypertensive patients and 27 normotensive subjects were studied. Maximal sodium-proton exchange activity was determined by acidifying cell pH and measuring the initial rate of the net sodium-dependent proton efflux driven by an outward proton gradient. The transcript level of NHE-1 was measured by reverse transcription-polymerase chain reaction in comparison with a constitutively expressed reference gene (beta-actin). With the 100% confidence (upper) limit of the normotensive population as a cutoff point, a subgroup of 11 hypertensive patients had an abnormally high lymphocyte Na+/H+ exchange activity (group A). The activity of the exchanger was within the normal range in the remaining patients (group B). After 6 months of quinapril treatment the activity of the exchanger decreased to normal values (P < .001) in patients from group A, but remained unchanged in patients from group B. The NHE-1 mRNA expression was not modified with treatment neither in patients from the group A, nor in patients from the group B. These results suggest that chronic angiotensin enzyme inhibition with quinapril abolishes Na+/H+ exchange overactivity present in lymphocytes from a subgroup of hypertensive patients. This effect appears to be independent of changes in the expression of the mRNA encoding for the NHE-1 isoform of the exchanger.