1. The effects of pinacidil (25 mg, sustained release formulation) a) on systemic (arterial pressure, cardiac output) and regional (brachial and carotid arteries' diameters and flows) haemodynamics (pulsed Doppler techniques), b) on sympathetic (plasma noradrenaline) and renin-angiotensin (plasma renin activity) systems, and c) on atrial natriuretic factor have been investigated and compared with those of a placebo during the 12 h period following oral administration in a randomized, double-blind and cross-over study performed in six healthy volunteers. Simultaneously, the plasma levels of pinacidil and of its active metabolite, pinacidil N-oxide, were determined. 2. As compared with placebo, pinacidil decreased systemic vascular resistance and arterial blood pressure but cardiac output was not modified. 3. Pinacidil significantly increased brachial and carotid arteries' diameters (by 7 and 8% respectively) and flows (by 60 and 17% respectively) and decreased forearm vascular resistance (by 43%). Thus, pinacidil dilates both large and small arteries, increases large vessels' compliance and redistributes blood flow towards the muscular vascular bed. These effects peaked at 4 h and their duration at the brachial level was 8 h. 4. Pinacidil administration resulted in a stimulation of both sympathetic (increases in heart rate and plasma noradrenaline) and renin-angiotensin systems, and induced a transient increase in atrial natriuretic factor. 5. The duration of pinacidil haemodynamic effects at the brachial level is consistent with the pharmacokinetic data which show that pinacidil and pinacidil N-oxide plasma levels almost plateaued between 3 and 8, and 2 and 8 h respectively after oral administration of the sustained release formulation used.
Adult Arteries