Shuichi Shigetomi

原発性アルドステロン症に対するTrilostane (MWD-1822) の効果

Six patients with primary aldosteronism (PA), one with idiopathic hyperaldosteronism (IHA), one with glucocorticoid responsible hyperaldosteronism (GRHA) and eight with essential hypertension (EH) were treated with trilostane (MWD-1822) (4 alpha, 5-epoxy-17 beta-hydroxy-3-oxo-5 alpha-androstane-2 alpha-carbonitrile), an inhibitor of adrenal steroid biosynthesis, for 9-47 days with a daily dose of 30-960 mg. Blood pressure decreased slightly and gradually from 30 min. to 360 min, plasma aldosterone (PAC) and cortisol concentration (F) decreased, and plasma dehydroepiandrosterone concentration (DHEA) increased 120 min. after the administration of a single dose of 120 mg of trilostane. In the patients with PA, IHA and GRHA on long term therapy with trilostane, blood pressure decreased, PAC and F were depleted, serum improved within normal limits and DHEA increased, but plasma progesterone concentration (Prog.) changed variously and plasma renin activity (PRA) remained suppressed. In the patients with EH, systolic pressure decreased in 5 out of 8 (under - 20 mmHg), and diastolic pressure decreased in 3 out of 8 (under - 10 mmHg), DHEA increased in all, but the changes in serum potassium, PAC, F, Prog. and PRA were various. There was no remarkable reaction after the administration of trilostane. It is concluded that trilostane is an effective inhibitor of 3-hydroxysteroid dehydrogenase in vivo and that it is useful in the treatment of primary aldosteronism and other hypertension due to hyperproduction of aldosterone.

Studies on the Blood Pressure Control Mechanism in Essential Hypertension

To elucidate the mechanism of blood pressure control in essential hypertension (EH), plasma norepinephrine concentrations (PNE), plasma renin activity (PRA), cardiac index (CI) and total peripheral resistance (TPR) were determined in normal subjects and those suffering from EH while resting and after standing with furosemide. The results were as follows: 1) PNE were 204 +/- 100 pg/ml (mean +/- S.D.) in normal subjects and 313 +/- 257 pg/ml in EH. PNE in EH were not significantly greater than in normal subjects, but in some patients with EH, PNE were above normal. 2) In both normal subjects and those suffering from EH, PNE and PRA showed a positive correlation (r = 0.45, p less than 0.05; r = 0.52, p less than 0.001; respectively). 3) In low renin EH, the response of PNE to the stimulation of standing with furosemide was significantly greater than in normal renin EH (p less than 0.05). 4) PNE in EH were independent of both TPR and CI. 5) There was a positive relation between PRA and CI (r = 0.44, p less than 0.05), and a slight negative relation between PRA and TPR (r = 0.36, 0.05 less than p less than 0.1). These results suggest that sympathetic nervous hypertonicity may be responsible for the activation of the renin-angiotensin system and that the interaction of both the sympathetic nervous system and the renin-angiotensin system may play an important role in the elevation of blood pressure. In low renin EH, the response of PNE to the stimulation of standing with furosemide may be normal and blood pressure may be controlled by both the sympathetic nervous system and the renin-angiotensin system.