1. Endogenous noradrenaline release from washed platelets incubated under resting conditions and in the presence of thrombin was examined in 14 normal subjects and 10 subjects with type 1 (insulin-dependent) diabetes. 2. Irreversible aggregation of platelets from both normal and diabetic subjects was induced by thrombin (0.3 unit/ml). Platelets from diabetic subjects were more sensitive than platelets from normal subjects, extents of aggregation being 89% and 76%, respectively ( P < 0.002). 3. Stimulation with thrombin (0.3 unit/ml) elicited marked platelet release of noradrenaline to the incubation medium in both normal and diabetic subjects. Supernatant noradrenaline concentrations obtained under thrombin-stimulated conditions did not significantly differ between normal and diabetic subjects. However, under resting conditions noradrenaline levels were significantly greater (+ 93%, P < 0.02) for diabetic than normal subjects. 4. Measurement of platelet noradrenaline contents after thrombin stimulation revealed no difference between normal and diabetic subjects. Under resting conditions, however, platelet noradrenaline levels were significantly lower (−46%, P < 0.02) for diabetic than normal subjects. Thus, in the diabetic subjects increased resting platelet efflux of noradrenaline is mirrored by a decreased platelet noradrenaline content. 5. A consequence of increases in resting catecholamine efflux may be enhanced platelet activity resulting in increased platelet aggregation.
1. We have used high-performance liquid chromatography with electrochemical detection to measure plasma and platelet catecholamines in 24 normal subjects. 2. In the same subjects platelet function was assessed by measuring platelet aggregation in response to adenosine 5′-pyrophosphate, thrombin, adrenaline and collagen. Platelet sensitivity to prostacyclin was also examined. 3. Platelet noradrenaline showed a positive correlation with extent of aggregation induced by ‘low-dose’ collagen (1 μg/ml). No correlation was seen at the higher collagen concentration. 4. Platelet noradrenaline content also correlated with sensitivity of platelets to prostacyclin. High platelet noradrenaline concentrations appeared to result in decreased sensitivity to prostacyclin. 5. No other correlations were observed. 6. These data suggest that platelet noradrenaline rather than plasma levels may be involved in modifying platelet function in vivo. Local release of platelet catecholamines may affect the platelet/vessel wall interaction, the primary physiological step in platelet activation.
1. Using high-performance liquid chromatography with electrochemical detection, we have studied the release of endogenous catecholamines from washed platelets induced to aggregate by ADP and thrombin. 2. Washed platelets exhibit irreversible aggregation with 10 μmol/l ADP and 0.3 unit of thrombin/ml, extents of aggregation being 27% and 76% respectively. 3. ADP (10μmol/l) increased noradrenaline release to the medium by 20% and adrenaline by 28%. As observed with aggregation, 0.3 unit of thrombin/ml produced a more marked effect on release than ADP, noradrenaline and adrenaline being increased by 570% and 169% respectively. 4. Values for platelet noradrenaline content were found to mirror those for the release from platelets induced by thrombin. 5. A correlation was observed between catecholamine release and the concentration of thrombin present in incubations. These data reflect the changes observed with platelet aggregation. 6. This is the first study to determine catecholamine release from platelets by direct measurement. Local catecholamine release after platelet aggregation in vivo may have important consequences for tissue perfusion.