Antihypertensive treatment with verapamil and amlodipine. Their effect on the functional autonomic and cardiovascular stress responses.

Abstract

Many biological and psychological factors induce haemodynamic and extra-cardiovascular functional changes mediated by the autonomic nervous system. Pharmacological blood pressure reduction, as a neurovegetative stimulus, can change the arousal of the sympathetic nervous system. We evaluated the effects of two calcium channel blockers, verapamil and amlodipine, both administered as monotherapies, upon the sympathetic stress response in 23 randomized mild-to-moderate essential hypertensives (161 +/- 2/98 +/- 1 mmHg). Patients performed four stress tests (mental arithmetic, colour word Stroop, cold pressor and handgrip) while extracardiovascular and haemodynamic functions were assessed non-invasively at every heart beat, during baseline, stress and recovery phases. The sympathetic response was evaluated by computing the 'area-under-the-curve' (value x time) measured during the psychophysiological session. The session was repeated at run-in, after placebo and during treatment. After one month's treatment, baseline blood pressure was significantly reduced in patients treated with amlodipine (139 +/- 1/84 +/- 1 mmHg; P < 0.001) and verapamil (140 +/- 2/85 +/- 1 mmHg; P < 0.001). The emotional arousal (frontalis muscular contraction, skin conductance) was unchanged, but the cutaneous vascular response was reduced (P < 0.05) in patients treated with verapamil. No changes in systolic or diastolic blood pressure were detectable, but amlodipine increased the heart rate response (P < 0.05). In contrast, verapamil reduced the heart rate (P < 0.05) without depressing the cardiac output response, which was increased with amlodipine (P < 0.05). Total vascular resistance was significantly (P < 0.001) reduced with both the treatments. Consequently, functional cardiac load, expressed by pressure-rate product and cardiac power, was significantly enhanced with amlodipine and reduced with verapamil. In conclusion, the abnormal sympathetic stress response, which characterizes the hypertensive patient, might be affected by the choice of medication. Verapamil in particular, moderated emotional arousal, the vasoconstrictive response and reduced cardiac load without lowering cardiac output demands. In contrast, in patients treated with amlodipine, in whom the cardiac output response was increased, the pattern was reversed and the functional cardiac load was also increased.