Inactive renin and prostaglandin E2 production in hyporeninemic hypoaldosteronism

To ascertain whether inactive renin (IR) might predominate in the syndrome of hyporeninemic hypoaldosteronism (HH) and whether the production of prostaglandin E2 (PGE2), a potent stimulus for renin release, might be decreased, we measured PRA, active renin (AR), and IR by the acid activation method and urinary PGE2 in 10 patients with HH. In contrast to uniformly low levels of PRA (0.6 +/- 0.2 ng/ml . h) and AR (2.7 +/- 0.6), IR was either normal or elevated (14.7 +/- 2.2 in HH; 11.8 +/- 1.1 in 28 normal subjects) and the IR to AR ratio was markedly increased (8.5 +/- 2.0 vs. 3.4 +/- 0.5; P < 0.05). Urinary PGE2 was decreased in 4 patients but was in the normal range in 5 other patients with HH. In 16 human volunteers, PG inhibition with indomethacin led to a significant decrease in AR (P < 0.05) but not in IR, and the IR to AR ratio increased 2-fold (P < 0.02). The data suggest that HH is a disease involving the defective conversion of IR to AR rather than impaired total renin production. In some patients, PG deficiency may contribute to the development of HH.