INCREASED NA-H+ EXCHANGE IN RED-BLOOD-CELLS OF PATIENTS WITH PRIMARY ALDOSTERONISM()

We measured Na+-H+ exchange as the amiloride-inhibited fraction of Hefflux from red blood cells into a sodium-containing medium (pH(o) 7.9 5 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-produc ing adrenal adenoma, 12 drug-free essential hypertensive patients, and 12 healthy control subjects. Red blood cell Na+-H+ exchange was incre ased in patients with primary aldosteronism similarly to the mean exch anger velocity in essential hypertensive patients compared with values in healthy subjects (334+/-25 and 310+/-29 versus 139+/-21 mu mol H+/ L cells per minute, respectively; P<.001 and .01). The kinetic paramet ers of Na+-H+ exchange returned to normal on day 2 after removal of th e aldosterone-producing mass. K-m for [Na+](o) was not affected by ald osterone, whereas K-m for [H+](i) was decreased in patients with prima ry aldosteronism. The kinetic characteristics did not differ in essent ial hypertensive patients and control subjects. Protein kinase C inhib ition in vitro by calphostin C (60 nmol/L) increased K-m for [H+](i) a nd 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, for both H+ and Na+. W e conclude that aldosterone stimulates red blood cell Na+-H+ exchange by a nongenomic mechanism that augments the exchanger affinity to Naand H+. In primary aldosteronism, protein kinase C and calmodulin seem to have synergistic stimulatory effects on red blood cell Na+-H+ exch ange, and both increase the affinity of the exchanger to H+, while the ir effect on Na+ binding is opposite.