Effect of verapamil sustained-release on the sympathetic nervous system response to isometric stress in patients with essential hypertension: a pilot study in Turkish patients

Abstract

Background: Stress and sympathetic nervous system activation play a major role in the pathogenesis of essential hypertension. Recent data suggest that the calcium channel blocker verapamil, in addition to its antihypertensive effects, can alter the level of norepinephrine released during stress. Objective: The purpose of this study was to examine the effects of verapamil sustained-release (SR) on the sympathetic nervous system response to stress in patients with essential hypertension. Methods: Patients with essential hypertension (diastolic blood pressure > 90 mm Hg and systolic blood pressure > 140 mm Hg) whose blood pressure was inadequately controlled or uncontrolled were enrolled in the study. Secondary hypertension was ruled out by routine biochemical, endocrine, and radiologic tests. After a 15-day washout period during which all previous anti-hypertensive medication was discontinued, blood pressure, heart rate, and serum norepinephrine levels were measured at rest and in response to stress (ie, isometric exercise). Patients began treatment with verapamil SR at dosages recommended in the Sixth Report of the Joint National Committee for the Prevention, Diagnosis, Evaluation, and Treatment of High Blood Pressure (240 mg/d for stage I hypertension and 480 mg/d for stage II and stage III hypertension). After 4 weeks of treatment, blood pressure, heart rate, and norepinephrine levels were measured again at rest and in response to stress. Results: Thirteen patients (9 women and 4 men) were enrolled; 9 patients completed the study. Three patients were lost to follow-up and 1 was noncompliant. Verapamil SR significantly lowered norepinephrine levels both at rest and in response to stress ( P < 0.01), and reduced the increase in norepinephrine levels after isometric exercise. Conclusion: These results suggest that in this small sample of Turkish patients, verapamil SR significantly diminished the sympathetic nervous system response to stress by decreasing norepinephrine levels. This property may make verapamil SR especially useful when there is a need for decreased sympathetic activity (and thereby, a reduction in oxygen consumption) as well as other antihypertensive effects, such as in patients with coronary heart disease.