Influence of a single dose of nitrendipine on whole blood platelet activity in healthy subjects.

The aim of this study was to examine whether therapeutical doses of nitrendipine influence platelet function. In eight healthy subjects, the platelet aggregation response to collagen in whole blood and platelet-rich plasma (PRP) was monitored over 12 h after single administration of 40 mg nitrendipine given orally and was strongly inhibited between 60-83% (0.3 microgram/ml collagen) versus baseline at the third and fourth hour. Stimulated thromboxane formation from exogeneous arachidonic acid decreased almost continuously, with lowest levels at the 12th hour. Basal thromboxane remained below 25 pg/ml, but platelet factor 4 increased to more than twice the baseline level in the fourth hour, presumably reflecting adrenergic counterregulation of hypotensive effects. These preliminary data show that therapeutic drug concentrations of nitrendipine inhibit platelet function. Therefore, calcium channel blockers may be of therapeutical value in the treatment of prethrombotic states with primary platelet hyperactivity as present, for example, in diabetes mellitus.

Nitrendipine-stimulated release of prostacyclin-like substance in normal and atherosclerotic animals.

Nitrendipine (Bayotensin) is a dihydropyridine derivative that appears to preferentially dilate peripheral vessels by a cellular mechanism similar to those found with other calcium blocking agents. In this study nitrendipine when infused (0.2-0.3 mg/kg i.v.) into anaesthetized cats caused a release of a substance disaggregating platelet clumps which had adhered to blood superfused collagen strip. The appearance of this unstable disaggregating substance was prevented by the pretreatment of cats with acetylsalicylic acid (50 mg/kg i.v.). In atherosclerotic rabbits nitrendipine stimulated release of prostacyclin-like substance without effect on proaggregatory concentrations of arachidonic acid and adenosine diphosphate. In rats nitrendipine inhibited the development of atherosclerotic changes in the aorta evoked by the atherogenic diet with ergocalciferol (vitamin D2). It is suggested that nitrendipine may promote formation of prostacyclin in arteries and inhibit the development of atherosclerosis.