Studies on the clinical pharmacology of prazosin. I: Cardiovascular, catecholamine and endocrine changes following a single dose

Abstract

1 Cardiovascular, catecholamine and neuroendocrine changes were studied following administration of prazosin to ten normal subjects. In response to a fall in standing blood pressure from 87±5 (s.d.) mmHg to 49±20 (P < 0.01) heart rate (measured by continuous ECG monitoring) rose from 81±11 to 118±20 (P < 0.01). Five of the ten subjects sustained their tachycardia on standing and developed at most mild symptoms. In the other five, tachycardia suddenly gave way to bradycardia and they became syncopal.

2 In the supine position, when blood pressure was not significantly different from control, plasma noradrenaline concentration (nmol/l) was 2±0.5 compared with a control value of 1.2±0.3 (P < 0.01). In response to standing hypotension plasma noradrenaline was 4.2±2.7 compared with a standing control value of 1.9±0.4 (P < 0.02).

3 Four hours after taking prazosin five of the subjects stood for 30 min and blood was drawn for plasma renin activity (PRA). Blood pressure at this time was 15 mmHg below control (P < 0.02). PRA (ng ml^-1 h^-1) was 6.4±2.3 compared with time matched placebo control of 1.4±0.8 (P < 0.01).

4 At the same time as the PRA sampling, plasma cortisol was 15.6±2.6 μg/100 ml during hypotension and 8.2±3.9 following placebo (P < 0.01). Growth hormone was 1.4±0.3 ng/ml during hypotension and 1.0±0.2 following placebo (P < 0.01). Prolactin did not rise significantly during hypotension induced by prazosin.

5 Isoprenaline infusion produced the same change in heart rate during the time of maximum prazosin action as when given alone.

6 It is concluded that these observations are not in keeping with earlier reports that prazosin lowers blood pressure without producing a reflex increase in heart rate or renin release. Nor are these findings in keeping with current theories of the mechanism of action of prazosin which variously suggest that noradrenaline concentration should not increase, or that the heart is incapable of responding to an adrenergic stimulus in the presence of prazosin.