Dextran-70 inhibits equine platelet aggregation induced by PAF but not by other agonists.
Dextrans of mean molecular weight 70 kDa (dextran-70) have had clinical use as anti-thrombotics in man. A major part of the anti-thrombotic action is mediated via inhibition of platelet function. Greatorex (1975, 1977) treated thromboembolic colic in horses with infusions of dextran-70 and reported a 90% recovery rate, but this treatment is nonetheless rarely used. We have used an in vitro method to examine the effect of dextran-70 on equine platelet suspensions, in the hope that understanding the mechanism of action of dextran-70 might lead to the development of alternative therapeutic agents. The effects of dextran-70 on equine platelets occurred immediately in vitro with an initial activation and shape change. Subsequent assessment of aggregation revealed a dose-dependent specific inhibition of platelet-activating factor (PAF)-induced aggregation, significant in rate of aggregation at dextran-70 concentrations >40 g/l (P<0.05) and in extent of aggregation at dextran-70 concentrations >50 g/l (P<0.05). Pre-incubation with 60 g/l dextran-70 significantly inhibited the rate and extent of aggregation in response to PAF (1 nmol/l) (P<0.001 and P = 0.003, respectively) but this was not dependent on the duration of pre-incubation (from 0 to 150 min). No effects were seen when the agonist was adenosine 5'-diphosphate (200 nmol/l), collagen (10 mg/l), 5-hydroxytryptamine (100 micromol/l) or U44069 (600 nmol/l) (all P>0.1). Analysis of PAF concentration-aggregation curves after pre-incubation with 60 g/l dextran-70 indicated significant noncompetitive inhibition by dextran-70 (P<0.001 for rate and extent of aggregation). The ability of dextran-70 to inhibit responses of equine platelets to PAF is probably an important component of its beneficial effect as an anti-thrombotic in colic cases.
Heath
M F
MF
University of Cambridge, Department of Clinical Veterinary Medicine, UK.
Evans
R J
RJ
Hayes
L J
LJ
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology; D003911:Dextrans / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006736:Horses / Q000097:blood*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology
D000925:Anticoagulants; D003911:Dextrans; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic; D012701:Serotonin; C028429:U 44069; D000244:Adenosine Diphosphate; D003094:Collagen