Angiotensin II can induce and potentiate shape change in human platelets: effect of losartan.
Platelet shape change (PSC) is an early phase of platelet activation that precedes platelet aggregation. This phase of platelet activation is essentially aspirin resistant. PSC was monitored, by measuring the median platelet volume (MPV) using a high resolution channelyser. Angiotensin (Ang) II, added in vitro, caused a significant (P = 0.004) increase in MPV in platelet rich plasma prepared from healthy subjects (n = 14). This increase in MPV was marked (>0.40 fl) in 57% (n = 8) of these subjects and was significantly inhibited (P<0.008) by losartan (a selective Ang II antagonist) at concentrations similar to those achieved in the circulation during treatment. Ang II also significantly enhanced sub-maximal PSC induced by ADP and serotonin in all subjects tested. Losartan significantly (n = 9; P<0.001) inhibited U46619 (a thromboxane A2 analogue)-induced PSC. These findings suggest that losartan, in addition to its blood pressure lowering action, has antiplatelet activity. This property may be clinically relevant because of the increased risk of vascular events in hypertensive patients.
Jagroop
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Department of Molecular Pathology and Clinical Biochemistry, Royal Free and University College Medical School (University of London), Royal Free campus, London, UK.
Mikhailidis
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D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D012701:Serotonin / Q000494:pharmacology
D000804:Angiotensin II; D012701:Serotonin; D000244:Adenosine Diphosphate; D019808:Losartan; D007213:Indomethacin