Comparison of equimolar concentrations of iloprost, prostacyclin, and prostaglandin E1 on human platelet function

Abstract

Prostaglandins E1 and I2 (PGE1 and PGI2) have been shown to be potent inhibitors of platelet aggregation. We compared the antiaggregatory effect of equimolar concentrations of these two agents with that of a newly synthesized prostacyclin analogue, iloprost, and measured the effects of these agents on intracellular levels of cyclic adenosine monophosphate (cAMP) in human platelets. In addition, because the platelet inhibitory properties of prostanoids are associated with increased vasoactivity, we assessed the effects of each prostanoid on coronary flow in isolated perfused rat hearts. Concentrations ranging from 0.0001 mumol/L to 1 mumol/L of iloprost, PGI2, and PGE1 were incubated with either platelet-rich plasma or gel-filtered platelets. Greater than 90% inhibition of platelet aggregation in response to threshold concentrations of adenosine diphosphate (n = 6) and epinephrine (n = 6) was observed in all donors when 0.01 mumol/L iloprost, 0.1 mumol/L PGI2, and 1 mumol/L PGE1 were added to platelet-rich plasma. In gel-filtered platelets, at threshold concentrations of thrombin (n = 6), 90% inhibition was observed with 0.01 mumol/L iloprost. In contrast, similar inhibition to thrombin required 0.1 mumol/L PGI2, and with PGE1 it was never achieved in two donors. At 0.01 mumol/L of prostanoid, cAMP levels (n = 6) rose from a baseline value of 439 +/- 99 pmol/10(9) platelets to 1857 +/- 454 pmol/10(9) platelets for iloprost, 758 +/- 99 pmol/10(9) platelets for PGI2, and 692 +/- 199 pmol/10(9) platelets for PGE1. In addition, at 6 mumol/L, alterations in coronary flow (P greater than 0.05) were noted to be 127% of baseline values for iloprost (n = 5) and 153% for PGI2 (n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)