Effect of amlodipine on hemodynamic and endocrine responses to mental stress

Little is known about the effects of antihypertensive drugs on hemodynamic responses to mental stress. We studied 24 patients with mild-to-moderate hypertension in a double-blind random-sequence crossover study comparing placebo with amlodipine titrated up from 5 to 10 mg daily. After 1 month of treatment, the subjects performed 20 min of a frustrating cognitive task. At baseline before task, amlodipine significantly reduced systolic pressure (128.9 ± 8.2 mm Hg v 140.3 ± 10.7 mm Hg, P< .001), diastolic pressure (81.7 ± 7.7 mm Hg v 90 ± 7.5 mm Hg, P< .001), and total peripheral resistance (37.5 ± 15 v 45.6 ± 23.7 mm Hg/L/min, P< .05), while elevating baseline norepinephrine levels (2286 ± 731 pmol/L v 1788 ± 546 pmol/L, P< .001). Blood pressure during the stress task was significantly less with amlodipine than with placebo (systolic 142.3 ± 12.3 mm Hg v 150.9 ± 14.6 mm Hg, P< .001; diastolic 87.9 ± 8.4 mm Hg v 97.7 ± 9.3 mm Hg, P< .001), whereas norepinephrine was significantly higher (2754 ± 1007 pmol/L v 1970 ± 740 pmol/L, P< .001). There were no significant differences in cardiac output, plasma lipids or lipoproteins, or markers of platelet activation. Heart rate increased significantly during stress, but there was no significant difference between amlodipine and placebo either at baseline or during stress. Our conclusion is that amlodipine reduces blood pressure at baseline and during mental stress, but raises basal and stress-related plasma catecholamines. This finding may have implications for the recent controversy over the safety of calcium channel antagonists, and suggests the potential relevance of combining amlodipine with adrenergic blockers.