Effects of different dihydropyridine calcium antagonists on plasma norepinephrine in essential hypertension

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Abstract
The aim of this study was to compare the chronic effects of four dihydropyridine calcium antagonists with different pharmacologic characteristics, amlodipine, felodipine, lacidipine and manidipine, on blood pressure (BP), heart rate (HR) and plasma norepinephrine (NE) levels in patients with mild to moderate essential hypertension. After a 4-week placebo period, 60 patients of both sexes were randomly administered amlodipine 5–10 mg once daily (o.d.) (n = 15); felodipine 5–10 mg o.d. (n = 15); lacidipine 4–6 mg o.d. (n = 15); manidipine 10–20 mg o.d. (n = 15), for 24 weeks, according to a double blind, parallel group design. Initially, for the first 2 weeks, the lowest dose of each drug was used, then higher doses were administered if sitting diastolic blood pressure (DBP) was > 90 mmHg. BP, HR and plasma NE were evaluated at the end of the placebo and active treatment periods. NE was assessed at trough, at peak and after 12 h from drug ingestion. Administration of all four drugs reduced clinic BP to the same level after 24 weeks, whereas HR increased only with felodipine (+ 3.1 bpm; P < 0.05). Significant increases in plasma NE levels were observed after chronic therapy with amlodipine and felodipine (+ 34.9 and + 39.4% respectively; P < 0.01 versus placebo) but not with lacidipine (+ 7.1%, NS) and manidipine (+ 2.9%, NS). These findings suggest that sympathetic activation occurred during chronic treatment with amlodipine and felodipine, whereas manidipine and lacidipine did not increase plasma noradrenaline at the times measured. The reasons for this difference are unclear; they could be related to the different pharmacological characteristic of the two drugs, lacidipine and manidipine.