Interactions of Clonidine and Nifedipine in Moderately Severe Hypertensive Patients

In ten patients (age: 47–59 yr) with moderately severe essential hypertension, the humoral and hemodynamic effects of a 4‐day therapy with 2 × 75 μg clonidine, 2 × 20 mg nifedipine (slow‐release), and their combination were investigated and compared with baseline values. The following measurements were observed under clonidine (C), nifedipine (N), and on combination (C/N), respectively: heart rate fell significantly under C from a mean of 79 to 67/min ( P < .05), increased to 73/min after N ( P > .05) and fell again to 68/min under combination ( P < .05). Systolic blood pressure (Riva‐Rocci method) decreased from a mean of 184 to 171 (C), 168 (N) and 161 mm Hg (C/N), respectively ( P < .01). Diastolic blood pressure was also significantly altered (113 vs. 104 (C), 107 (N), and 100 mm Hg (C/N) ; P < .05). Stroke volume (ECHO) was not altered significantly (77 vs. 71 (C), 79 (N), and 80 mL (C/N), respectively), whereas cardiac output dropped from 5.9 to 4.9 L/min (C ; P < .05), increased to 5.7 (N ; P > .05), and dropped again to 5.3 L/min (C/N ; P > .05). Peripheral vascular resistance increased from a mean of 2091 to 2297 (C), fell to 1933 (N), and increased again to 2138 dyn/sec/cm −5 (C/N). Plasma norepinephrine levels fell from 440 to 281 (C ; P < .01), increased to 391 (N ; P > .05), and fell again to 404 pg/mL (C/N ; P > .05). PRA decreased significantly from a mean of 1.77 to 0.96 (C), increased to 2.11 (N ; P < .05), and was unchanged on combination (1.77 vs. 1.76 ng/mL/hr). Aldosterone levels fell after clonidine administration and combination therapy, but were unchanged after nifedipine administration. Epinephrine, vasopressin, and ANF showed no significant changes. This study showed that combined administration of low‐dose nifedipine and clonidine leads to a purely additive reduction in blood pressure and a compensation of the nifedipine‐induced increase in heart rate. The disadvantages of neurohumoral counter‐regulation of nifedipine therapy are neutralized by clonidine, testifying to the usefulness of combined therapy of low‐dose clonidine and nifedipine, which, in addition, is well tolerated .