Increased Na + -H + Exchange in Red Blood Cells of Patients With Primary Aldosteronism

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Abstract
We measured Na + -H + exchange as the amiloride-inhibited fraction of H + efflux from red blood cells into a sodium-containing medium (pH o 7.95 to 8.05) at pH i 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 μmol 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. K m for [Na + ] o was not affected by aldosterone, whereas K m 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 K m for [H + ] i and caused up to a 65% suppression of Na + -H + exchange (pH i 6.05 to 6.15), while diminishing K m 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 K m 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.