IMPAIRED RAPID MINERALOCORTICOID ACTION ON FREE INTRACELLULAR CALCIUMIN PSEUDOHYPOALDOSTERONISM

Earlier observations on impaired in vitro effects of aldosterone on ly mphocytic sodium and potassium pointed to the involvement of a defecti ve nongenomic rather than genomic effector in pseudohypoaldosteronism. In this study, we investigated nongenomic aldosterone action in five patients with pseudohypoaldosteronism with regard to a rapid increase of free intracellular calcium [Ca2+](i) in cultured nasal epithelial c ells, assumably reflecting calcium influx through calcium channels. Pa tients were defined by episodes of salt loss despite high plasma aldos terone and renin levels. Four unaffected members of the families and f our independent subjects served as controls. Considering an aldosteron e-induced increase of [Ca2+](i) by at least 10 nm as positive response , only 12% of cells from patients were responsive compared with 25% in normal subjects (P < 0.05). In terms of absolute changes, mean increa se of[Ca2+](i) was 1.6 +/- 1.1 nm in the patients (range - 1-4) and 9. 5 +/- 2.7 nm (P < 0.025) in the controls (range 1-25). Basal [Ca2+](i) was not different between both groups (167 +/- 5 vs. 169 +/- 8 nm, me an +/- SE). These findings show an impaired nongenomic mineralocortico id effector in patients with pseudohypoaldosteronism, which is in line with a defective sodium channel as shown recently by molecular clonin g, and also with the fact that the classical, genomic intracellular re ceptor is structurally normal in these patients.