[Mechanism of inhibition of aldosterone secretion by a Ca2+ channel blocker in patients with essential hypertension and patients with primary aldosteronism].

Three studies were conducted in order to investigate the suppressive effects of a calcium antagonist on aldosterone secretion and a possible mechanism. Study 1: A long-term (4 weeks) treatment with slow-release nifedipine (Nif), 40-60 mg/day, was performed in 9 in-patients with essential hypertension (EHT). Mean arterial pressure (MAP), plasma renin activity (PRA), plasma angiotensin II levels (pAII) and plasma aldosterone concentration (PAC) were determined before and after Nif treatment. Study 2: In another 7 in-patients with EHT, Nif treatment (40-60 mg, 7-10 days) was carried out to study its effect on aldosterone secretion in response to 2-hour ambulation, angiotensin II (AII) infusion (2.5 ng/kg/min, for 1-hour) and ACTH injection (2.5 mg i.v.). Study 3: The effects of Nif (40-60 mg/day, for 7-10 days) on MAP, PAC, serum potassium, potassium clearance (Ck) and changes in PAC or plasma cortisol levels in response to ACTH injection (2.5 mg i.v.) were studied in 6 in-patients with primary aldosteronism (PA). In patients with EHT, MAP was reduced significantly at 1 week and 4 weeks after the administration of Nif. PRA and pAII increased significantly, though the increase of PAC was not significant. In the low-renin EHT group, PAC was reduced significantly (Study 1). The increase of PAC in response to 2-hour ambulation or AII infusion was inhibited by Nif, but no inhibition of aldosterone response to ACTH was observed (Study 2). In patients with PA, Nif lowered MAP, PAC, and Ck, and elevated serum potassium concentration significantly. On the other hand, Nif had no effect on the aldosterone or cortisol response to ACTH (Study 3). These results indicated that the hypotensive effect of Nif is due in part to the inhibition of aldosterone secretion from the adrenal gland both in patients with EHT and in those with PA. Regarding the mechanism of the inhibition of aldosterone secretion by Nif, these data suggest that in patients with EHT, inhibition of the aldosterone response to AII is the most important factor, although it was not clear from this study whether Nif inhibits the potassium-induced aldosterone release or not. In patients with PA, ACTH-induced aldosterone secretion was not inhibited by Nif and the reduction of PAC is not likely via inhibition of AII action since the renin-angiotensin system is markedly suppressed. Reduced cytosolic calcium concentration in the adenomatous tissue by Nif may have something to do with the lowered aldosterone synthesis in PA.