Increased Na(+)-H+ exchange in red blood cells of patients with primary aldosteronism.

Abstract

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.

• Authors: W Koren, I Y Postnov, Y V Postnov
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 29 Issue 2 Pg. 587-91 (Feb 1997) ISSN: 0194-911X [Print] United States
• PMID: 9040443 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Calmodulin
• Naphthalenes
• Sodium-Hydrogen Exchangers
• Sulfonamides
• Aldosterone
• N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide
• Protein Kinase C
• calphostin C

Topics

• Adrenal Gland Neoplasms (complications)
• Adult
• Age Factors
• Aldosterone (metabolism)
• Blood Pressure
• Calmodulin (antagonists & inhibitors)
• Erythrocytes (drug effects, metabolism)
• Female
• Humans
• Hyperaldosteronism (blood, etiology, surgery)
• Hypertension (blood)
• In Vitro Techniques
• Male
• Middle Aged
• Naphthalenes (pharmacology)
• Protein Kinase C (antagonists & inhibitors)
• Sex Factors
• Sodium-Hydrogen Exchangers (blood, drug effects)
• Sulfonamides (pharmacology)
• Time Factors