Inhibition of whole blood platelet aggregation by nicardipine, and synergism with prostacyclin in-vitro.
Platelets are involved in the pathogenesis of vascular disease, and calcium channel blocking agents (CCB) such as nicardipine, are being used in the treatment of such disorders. CCB's are known to have minor anti-platelet actions from studies performed in platelet rich plasma (PRP). Recently it has become possible to study platelet aggregation in whole blood. The effects of nicardipine on whole blood platelet aggregation were studied in-vitro using the Clay-Adams Ultra Flo 100 whole blood platelet counter. Nicardipine inhibited aggregation to 0.5 micrograms/ml collagen, and 0.5 mM arachidonic acid in a dose dependent manner, but had minimal effects on aggregation to 10 microM ADP. Nicardipine also acted synergistically with prostacyclin to inhibit aggregation. The effect of nicardipine on generation of PGI2 and TxA2 from whole blood was studied. Nicardipine did not affect TxA2 production, but significantly increased PGI2 production at high concentration. The effect of nicardipine on vascular PGI2 production was also assessed using umbilical artery rings, but nicardipine had no effect on PGI2 production. This study confirms that CCBs have inhibitory actions on platelet aggregation, and this may be of value in the treatment of vascular disease.
Greer
I A
IA
Walker
J J
JJ
McLaren
M
M
Calder
A A
AA
Forbes
C D
CD
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D004357:Drug Synergism; D011464:Epoprostenol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D009529:Nicardipine; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D012016:Reference Values; D013928:Thromboxane A2 / Q000097:blood; D013929:Thromboxane B2 / Q000494:pharmacology
D000959:Antihypertensive Agents; D001095:Arachidonic Acids; D016718:Arachidonic Acid; D013929:Thromboxane B2; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D003094:Collagen; D009529:Nicardipine; D011464:Epoprostenol; D009543:Nifedipine