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The acute and chronic effects of nitrendipine on plasma catecholamines in hypertensive patients
H el-Beheiry1, N Ruedy, R A Wall
1Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver.
Objective:
To investigate the acute and chronic effects of nitrendipine on plasma catecholamines in hypertensive patients.
Design:
The variations in level of plasma noradrenaline and adrenaline were measured in the supine and standing positions before and after the initial dose, and after 12 weeks of nitrendipine therapy. Following a washout placebo period, treatment was initiated by a single 20 mg dose of nitrendipine. This was followed by a double-blind randomization into two groups: one receiving 10 mg nitrendipine twice daily, the other receiving 20 mg once daily.
Setting:
Clinical investigation unit, University Hospital (University of British Columbia site), Vancouver, British Columbia.
Patients:
Sixteen patients (seven males and nine females), mean age 51 years (range 27 to 63), with mild to moderate, uncomplicated hypertension.
Results:
Two hours after administration of the initial 20 mg nitrendipine dose to all patients, there was a significant fall in the supine and standing systolic and diastolic blood pressure - from 164 +/- 3/102 +/- 1 to 139 +/- 2/87 +/- 2 mmHg, and from 153 +/- 4/105 +/- 1 to 139 +/- 3/90 +/- 1 mmHg, respectively. The supine and standing heart rates were unchanged. After 12 weeks of nitrendipine therapy, blood pressure was reduced (2 h after the dose) to a similar extent as that seen after the initial dose. Acute and chronic nitrendipine administration significantly increased supine and standing noradrenaline, but not adrenaline. Two hours after the initial 20 mg dose, supine noradrenaline increased from 3404 +/- 585 to 4005 +/- 644 pmol/L and standing noradrenaline increased from 3769 +/- 609 to 5821 +/- 615 pmol/L. At the end of the 12 weeks of therapy, similar dose-dependent effects were observed 2 h after the dose, but not 12 or 24 h after the dose, in both groups. The percentage increase in noradrenaline produced by nitrendipine in the standing position was consistently greater than in the supine position.
Conclusions:
Chronic nitrendipine therapy results in a daily increase in plasma noradrenaline (2 h after the dose), and the effect is greater in the standing position.