Effects of nisoldipine on sympathetic activity, the renin-angiotensin-aldosterone system, and water-sodium-calcium metabolism in patients with essential hypertension.

The effects of nisoldipine (Bay k 5552), a long-acting Ca2+ antagonist, on sympathetic activity, the renin-angiotensin-aldosterone (RAA) system, the renal metabolism of water and electrolytes, and parathyroid hormone (PTH) were investigated following single dose and 4 weeks administration. The administration of nisoldipine led to the following results: 1. Mean arterial pressure (MAP) fell and heart rate slightly increased after the first dose, but did not show any appreciable change over 4 weeks treatment. 2. The urinary excretion of sodium, fractional excretion of sodium, plasma renin activity (PRA) and plasma noradrenaline concentration (pNA) were elevated initially, but the trend was to return to pretreatment levels after 4 weeks treatment. 3. A decrease in plasma aldosterone concentration was observed from the commencement of treatment. 4. Urinary excretion of calcium, fractional excretion of calcium and 24-h urine volume (UV) increased from the beginning, and maintained elevated levels after 4 weeks treatment. A decrease in body weight was also observed. 5. Plasma Ca2+ concentration did not change significantly throughout the treatment period, but PTH was decreased significantly both after 1 week and 4 weeks. 6. The percent changes in MAP (% delta MAP) after 4 weeks showed a significant negative correlation with pretreatment levels of MAP and the increment of UV (delta UV), as well as a positive correlation with pretreatment PRA or pNA levels. These findings suggest that in addition to its direct vasodilative effect, suppression of sympathetic activity and the renin-angiotensin-aldosterone system, reduction in body fluid and sodium, and a decrease in PTH and the related calciuresis may contribute to the hypotensive mechanism of nisoldipine.