Increased Na(+)-H+ exchange in red blood cells of patients with primary aldosteronism.
We measured Na(+)-H+ exchange as the amiloride-inhibited fraction of H+ efflux from red blood cells into a sodium-containing medium (pHo 7.95 to 8.05) at pHi values of 6.05 to 6.15, 6.35 to 6.45, 6.95 to 7.05, and 7.35 to 7.45 in 12 drug-free patients with primary aldosteronism before and after excision of histologically proven aldosterone-producing adrenal adenoma, 12 drug-free essential hypertensive patients, and 12 healthy control subjects. Red blood cell Na(+)-H+ exchange was increased in patients with primary aldosteronism similarly to the mean exchanger velocity in essential hypertensive patients compared with values in healthy subjects (334 +/- 25 and 310 +/- 29 versus 139 +/- 21 mumol H+/L cells per minute, respectively; P < .001 and .01). The kinetic parameters of Na(+)-H+ exchange returned to normal on day 2 after removal of the aldosterone-producing mass. Km for [Na+]o was not affected by aldosterone, whereas Km for [H+]i was decreased in patients with primary aldosteronism. The kinetic characteristics did not differ in essential hypertensive patients and control subjects. Protein kinase C inhibition in vitro by calphostin C (60 nmol/L) increased Km for [H+]i and caused up to a 65% suppression of Na(+)-H+ exchange (pHi 6.05 to 6.15). while diminishing Km for [Na+]o in red blood cells of patients with primary aldosteronism. The calmodulin antagonist W-13 (60 mmol/L) decreased exchanger velocity and increased Km for both H+ and Na+. We conclude that aldosterone stimulates red blood cell Na(+)-H+ exchange by a nongenomic mechanism that augments the exchanger affinity to Na+ and H+. In primary aldosteronism, protein kinase C and calmodulin seem to have synergistic stimulatory effects on red blood cell Na(+)-H+ exchange, and both increase the affinity of the exchanger to H+, while their effect on Na+ binding is opposite.
Koren
W
W
Central Research Laboratory, Ministry of Public Health, Moscow, Russia.
Postnov
I Y
IY
Postnov
Y V
YV
D000310:Adrenal Gland Neoplasms / Q000150:complications; D000328:Adult; D000367:Age Factors; D000450:Aldosterone / Q000378:metabolism; D001794:Blood Pressure; D002147:Calmodulin / Q000037:antagonists & inhibitors; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000097:blood* / Q000209:etiology / Q000601:surgery; D006973:Hypertension / Q000097:blood; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012737:Sex Factors; D017923:Sodium-Hydrogen Exchangers / Q000097:blood* / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors
D002147:Calmodulin; D009281:Naphthalenes; D017923:Sodium-Hydrogen Exchangers; D013449:Sulfonamides; D000450:Aldosterone; C033772:N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide; D011493:Protein Kinase C; C058819:calphostin C