Angiotensin converting enzyme inhibition corrects Na+/H+ exchanger overactivity in essential hypertension.
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.
Fortuño
A
A
Vascular Pathophysiology Unit, School of Medicine, University of Navarra, Pamplona, Spain.
Tisaire
J
J
López
R
R
Bueno
J
J
Díez
J
J
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy; D007546:Isoquinolines / Q000627:therapeutic use*; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000077583:Quinapril; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D017923:Sodium-Hydrogen Exchangers / Q000096:biosynthesis*; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D012333:RNA, Messenger; D017923:Sodium-Hydrogen Exchangers; D044005:Tetrahydroisoquinolines; C069139:growth factor-activatable Na-H exchanger NHE-1; D000077583:Quinapril