1. Plasma and platelet free catecholamine concentrations were measured in 22 normal subjects and in 10 treated and 11 untreated patients with heterozygous familial hypercholesterolaemia. 2. Plasma noradrenaline concentrations were significantly higher in both treated and untreated hypercholesterolaemic patients than in normal subjects. Adrenaline concentrations did not differ. 3. Platelet noradrenaline levels were higher in untreated hypercholesterolaemic patients than in normal subjects. 4. Positive correlations between the plasma noradrenaline concentration and the platelet noradrenaline concentration were observed in both normal subjects and hypercholesterolaemic patients. 5. Combining the data for normal subjects and hypercholesterolaemic patients revealed that the plasma noradrenaline concentration correlated positively with the plasma cholesterol concentration. The platelet noradrenaline concentration was also found to correlate with the plasma cholesterol concentration. 6. Our results suggest that an increased plasma cholesterol concentration may be associated with increased sympathetic nervous system activity as indicated by elevated plasma and platelet noradrenaline levels. Increases in circulating catecholamines may contribute to the platelet hyperaggregability seen in familial hypercholesterolaemia.

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.

1. We have used high-performance liquid chromatography with electrochemical detection to measure content of adrenaline and noradrenaline in platelets in 13 normal subjects at rest. 2. Subjects were exercised to raise plasma catecholamine levels and promote the platelet release reaction. 3. There was a significant positive correlation between plasma noradrenaline concentrations and platelet noradrenaline content. 4. Platelet/plasma concentration ratios were 1855 for noradrenaline and 268 for adrenaline at rest and 473 and 152 respectively after exercise. 5. Plasma noradrenaline levels positively correlated with age. 6. Determination of platelet factors released to the plasma showed increases of β-thromboglobulin and platelet factor 4 with exercise, whereas thromboxane B 2 remained unchanged. No change in platelet catecholamine levels occurred with exercise and no correlations were observed between platelet catecholamines and released platelet factors. 7. These data suggest that plasma catecholamine levels influence platelet content and that noradrenaline and adrenaline are concentrated in platelets.

1. The mode of action of acipimox (5-methyl-pyrazine carboxylic acid 4-oxide), an hypotriglyceridaemic agent, was examined in human adipose tissue and intestinal mucosa. 2. The rates of release of fatty acids and glycerol from human adipose tissue were measured in vitro. The release of fatty acids and glycerol from adipose tissue maximally stimulated by isoprenaline (10 −5 mol/l) fell by 40 and 25% respectively ( P <0.025 and P <0.025) in the presence of acipimox (10 −5 mol/l). In submaximally stimulated adipose tissue (isoprenaline 10 −7 mol/l) acipimox (10 −4 mol/l) fully inhibited release of fatty acids ( P <0.05) and glycerol ( P <0.025) to basal rates. In unstimulated adipose tissue acipimox (10 −3 mol/l) reduced the rate of glycerol release ( P <0.05), but not the rate of fatty acid release. 3. Cholesterol synthesis in jejunal mucosa was measured in vitro by the incorporation of [2- 14 C]-acetate into sterols. Addition of cholesterol to the incubation reduced [2- 14 C]acetate incorporation into sterols from 8.7 ± 2.1 (mean ± standard error) to 3.7 ± 1.0 pmol h −1 mg −1 of tissue ( P <0.01). Acipimox at 10 −4 -10 −2 mmol/l had no consistent effect on cholesterol synthesis. 4. Acipimox appears to exert its main hypolipidaemic effect by reducing lipolysis and free fatty acid flux to the liver, thereby reducing the precursor pool size of very low density lipoprotein (VLDL)-triglyceride and VLDL synthesis.