Platelet Na(+)-H+ exchanger activity in normotensive and hypertensive subjects: effect of enalapril therapy upon antiport activity.
OBJECTIVE
Primary hypertension has been reported to be associated with an enhancement of Na(+)-H+ exchange. However, details of the kinetic properties of the Na(+)-H+ exchanger in hypertensives and its dependence upon age and gender in normotensives are unknown.


METHODS
We determined the activity of the platelet Na(+)-H+ exchanger in 20 normotensives and 26 untreated primary hypertensives.


METHODS
In eight hypertensive individuals antihypertensive treatment was interrupted for 1 week. Treatment for 6 weeks with a daily single dose of 10 mg enalapril decreased mean arterial pressure to 105.7 +/- 11.6 mmHg.


METHODS
Platelets were loaded with the intracellular pH (pHi) indicator 2'-7'-bis-carboxyethyl-5(6)-carboxyfluorescein (BCECF) and acidified by propionic acid. Initial velocities of pH recovery were determined and used for calculation of maximum velocity (Vmax), baseline pHi and the pHi value for half maximal activation (pH0.5) of the Na(+)-H+ exchanger in each individual.


RESULTS
In normotensives, Vmax averaged 0.05 +/- 0.01 dpHi/min independently of age, gender and actual diastolic blood pressure. In hypertensives, two different subgroups were defined bearing either low or high Na(+)-H+ exchange activity. Values of pHi and pH0.5 were identical in all subgroups irrespective of Vmax. The twofold enhancement of Na(+)-H+ exchange in the second group was preserved in thrombin-stimulated platelets. Vmax values remained unaffected by enalapril treatment.


CONCLUSIONS
Enhanced Na(+)-H+ exchange activity in hypertensives is primarily characterized by an increase in Vmax. This enhancement is refractory to antihypertensive treatment and therefore appears to be a relatively fixed parameter.
Rosskopf
D
D
Max-Planck-Institut für Biophysik, Frankfurt/Main, Germany.
Siffert
G
G
Osswald
U
U
Witte
K
K
Düsing
R
R
Akkerman
J W
JW
Siffert
W
W
D000367:Age Factors; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D005452:Fluoresceins; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D005452:Fluoresceins; D017923:Sodium-Hydrogen Exchangers; D004656:Enalapril; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein