Proceedings of The Physiological Society
Kings College London (2005) J Physiol 565P, C179
Diabetic plasma prevents the increase in platelet aggregation seen in a rat model of diabetes
Queen, Lindsay R; Paul, William ; Page, Clive P; Ferro, Albert ;
1. GKT School of Medicine (Cardiovascular Division), King's College London, London, United Kingdom. 2. Sackler Institute for Pulmonary Pharmacology, King's College London, London, United Kingdom.
Figure 1. Aggregation of washed platelets from control (solid line) and STZ-treated (broken line) rats
Figure 2. Graphs show aggregation of platelets from control rats (panel A) and platelets from STZ-treated rats (panel B) suspended in plasma from control rats (solid line) or plasma from STZ-treated rats (broken line)
Thrombotic disease, a major complication in diabetic patients, is associated with increased platelet reactivity1. However, some data from experimental animal models suggest that platelets in diabetes are similarly or less reactive than control platelets2,3. In vivo we have previously reported that platelet aggregation is less in streptozotocin (STZ) diabetic rats as compared to control rats4. In this study, we examined aggregation responses in vitro in both washed platelets and platelets in the presence of plasma in this same model. Male Wistar rats were rendered diabetic by intraperitoneal injection of STZ 50mg/kg (n=6). Control rats were injected with saline (n=6). Experiments were performed 21 days post-injection. Blood glucose concentration was 6.3 ± 0.2mM in controls and 28.3 ± 0.8mM in STZ-treated rats (P<0.01). Rats were anaesthetised with urethane 1.5g/kg i.p. and blood was collected from the abdominal aorta into trisodium citrate then centrifuged to obtain platelet-rich plasma (PRP). Platelets were obtained by centrifugation of PRP and resuspended in either Ca++-free Tyrode solution, platelet-poor plasma (PPP) from control rats or PPP from STZ-treated rats. Responses were measured to ADP (0.3-30μM) using standard Born aggregometry. Data are mean ± SEM. Statistical analysis was by two-way ANOVA with P<0.05 taken as significant. ADP-induced aggregation was increased in washed platelets from STZ-treated rats as compared to controls (Fig.1). In contrast, platelets from control or STZ-treated rats resuspended in PPP from STZ-treated rats exhibited reduced aggregation, as compared with the same platelets resuspended in PPP from control rats (Fig.2). In conclusion, platelets from STZ-treated rats are inherently more sensitive to ADP-induced aggregation than platelets from controls. However, in the presence of plasma from STZ diabetic rats, platelet responsiveness is reduced, suggesting that one or more factors are present in diabetic plasma which inhibit this aggregation. The nature of such factors remains to be elucidated.
Where applicable, experiments conform with Society ethical requirements