SIN-1 partially and RGDS totally counteracts platelet aggregation as assessed in vitro by two independent whole blood methods.
The cyclic GMP stimulant SIN-1 and the GP IIB/IIIA receptor antagonist RGDS were compared with regard to platelet antiaggregatory effects as measured in vitro by filtragometry and by whole blood aggregometry. In filtragometry platelet aggregation is measured as the time to partial occlusion of a filter in the test unit. Beta-thromboglobulin concentrations increased over the filter (p < 0.002) indicating that in filtragometry part of the mechanism of aggregation could be platelet activation across the filter. In whole blood aggregometry platelet aggregation is induced by a chemical stimulant. As tested in blood from healthy volunteers, linear dose-effect relations were found with both methods, for SIN-1 in the 10(-7)-10(-6) M range (p < 0.02, filtragometry and p < 0.05, whole blood aggregometry) and for RGDS in the 10(-5)-10(-4) M range (p < 0.0001, filtragometry and p < 0.02, whole blood aggregometry). At the highest dose RGDS totally counteracted platelet aggregation in both test systems. Maximal SIN-1 platelet antiaggregatory effects were less (p < 0.04, filtragometry and p < 0.01, whole blood aggregometry) than for RGDS. SIN-1 concentrations in the 10(-4) M range had no further antiaggregatory effects. In conclusion, with two principally different methods for the assessment of whole blood platelet aggregation, SIN-1 was found to be a partial antagonist while RGDS a total antagonist.
Karlberg
K E
KE
Karolinska Institute, Department of Medicine, Huddinge University Hospital, Sweden.
Chen
J
J
Egberg
N
N
Sylvén
C
C
D000595:Amino Acid Sequence; D004553:Electric Conductivity; D006801:Humans; D008969:Molecular Sequence Data; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*
D009842:Oligopeptides; D010975:Platelet Aggregation Inhibitors; C002385:linsidomine; C046617:arginyl-glycyl-aspartyl-serine; D008981:Molsidomine