THE HYPOTENSIVE EFFECT OF NISOLDIPINE - 24-HOUR BLOOD-PRESSURE PROFILE AND SERIAL ALTERATIONS OF RENAL AND HORMONAL FUNCTION

To investigate its hypotensive effect and mechanism of action, a long-acting calcium channel blocker, nisoldipine, was administered once daily for 12 days to eight subjects with essential hypertension. Daily changes in blood pressure and heart rate, as well as serial alterations in renal and hormonal function, were investigated. Nisoldipine significantly reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP) on days 2 and 12 of treatment (daytime SBP: from 161.6 +/- 4.0 mmHg to 141 +/- 6.1 mmHg and 131.1 +/- 4.7 mmHg, respectively; daytime DBP: from 100.4 +/- 3.1 mmHg to 90.1 +/- 4.8 mmHg and 81.8 +/- 4.0 mmHg; nocturnal SBP: from 151.2 +/- 8.6 mmHg to 132.0 +/- 2.0 mmHg and 121.6 +/- 1.6 mmHg; and nocturnal DBP: from 91.9 +/- 1.0 mmHg to 81.3 +/- 1.1 mmHg and 77.1 +/- 1.1 mmHg). The extent of fluctuation of SBP and DBP, as indicated by the standard error of the mean (SEM) calculated from the blood pressures of each subject, was significantly increased on day 2. There was a moderate increase in heart rate on day 2 and it returned to the pretreatment level on day 12. Urinary sodium excretion was transiently increased on day 4, and body weight decreased significantly after administration of nisoldipine. Plasma renin activity and urinary norepinephrine level were increased significantly on day 6 and returned to baseline on day 12. These results suggest that once-daily administration of nisoldipine decreases blood pressure quite rapidly and that stable blood pressure control is obtained within 2 weeks. The antihypertensive mechanism of this drug may be partly related to a reduction of baroreceptor sensitivity and a reduction of total body water and sodium, as well as to its direct vasodilatory action.