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 hy pertension in a double-blind random-sequence crossover study comparing plac ebo with amlodipine titrated up from 5 to 10 mg daily. After 1 month of tre atment, the subjects performed 20 min of a frustrating cognitive task. At b aseline before task, amlodipine significantly reduced systolic pressure (12 8.9 +/- 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 resist ance (37.5 +/- 15 v 45.6 +/- 23.7 mm Hg/L/min, P < .05), while elevating ba seline norepinephrine levels (2286 +/- 731 pmol/L v 1788 +/- 546 pmol/L, P < .001). Blood pressure during the stress task was significantly less with amlodipin e 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), whe reas 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 l ipoproteins, or markers of platelet activation. Heart rate increased signif icantly during stress, but there was no significant difference between amlo dipine and placebo either at baseline or during stress. Our conclusion is t hat amlodipine reduces blood pressure at baseline and during mental stress, but raises basal and stress-related plasma catecholamines. This finding ma y have implications for the recent controversy over the safety of calcium c hannel antagonists, and suggests the potential relevance of combining amlod ipine with adrenergic blockers. (C) 2000 American Journal of Hypertension, Ltd.