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 (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 mu mol 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, 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.