Nifedipine reduces thromboxane A2 production by platelets without changing aggregation in hypertensive pregnancy.
Platelet aggregation and thromboxane A2 generation were studied in hypertensive pregnant women using normotensive non-pregnant and pregnant controls. In hypertensive pregnancy, adrenaline- and adenosine diphosphate-induced platelet aggregation was at the non-pregnant level and lower than in normotensive pregnancy. Collagen-induced aggregation was at a lower level in hypertensive pregnancy than in both control groups. Thromboxane generation during spontaneous clotting and in platelet-rich plasma did not differ between the three groups. However, thromboxane generation was low during aggregation induced by small collagen concentrations in hypertensive pregnancy, but at higher collagen concentrations the difference between the groups disappeared. During nifedipine treatment (10 mg t.i.d.), aggregation and thromboxane production in platelet-rich plasma induced by the three stimuli remained unaltered in hypertensive pregnancy, while thromboxane synthesis during spontaneous clotting was reduced. In nifedipine-treated non-pregnant controls, only EC80 for adrenaline-induced aggregation decreased. In vitro, pharmacological concentrations of nifedipine inhibited platelet aggregation and thromboxane production. In conclusion, nifedipine reduces thromboxane generation in spontaneous clotting, without inhibiting platelet aggregation and thromboxane production in platelet-rich plasma in hypertensive pregnancy. Reduced aggregability of platelet ex vivo may reflect their continuous activation and desensitization in vivo in hypertensive pregnancy.
Manninen
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A
University of Tampere, Medical School, Finland.
D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count / Q000187:drug effects; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000097:blood* / Q000503:physiopathology; D013928:Thromboxane A2 / Q000096:biosynthesis* / Q000097:blood
D000959:Antihypertensive Agents; D013928:Thromboxane A2; D009543:Nifedipine