Platelet efflux of noradrenaline in patients with type 1 diabetes mellitus

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.

Efflux of Noradrenaline from Platelets in Normotensive Members of Hypertensive Families

1. Platelets have been used as a model of sympathetic neurons to study the storage of noradrenaline in normotensive individuals belonging to families with essential hypertension for at least two generations. 2. The initial efflux rate (k) of noradrenaline was determined in 44 young relatives (mean age 29.2 years), in 18 middle-aged relatives (mean age 46.7 years) and in 31 young controls with no known family history of essential hypertension (mean age 29.8 years). From the groups of relatives all those with definite hypertension had been excluded a priori. 3. k was significantly higher in the young relatives (22.7 ± 7.9) than in the middle-aged relatives (17.7 ± 6.4) and in the controls (15.6 ± 5.1). Of the relatives 27.3% had higher k values than any of the controls. A significant correlation was found between k and diastolic blood pressure in controls but not in young relatives.

Correlation Between Noradrenaline Fluxes, Metabolism and Compartmentalisation in Human Platelets

Summary(3H) noradrenaline was taken up by human platelets and partially converted into sulfoconjugated noradrenaline. This uptake was inhibited by drugs which have been previously shown to impair the uptake of 5-HT (ouabain, chlorimipramine) or the storage of 5-HT (tyramine, reserpine) by platelets. In addition, tyramine and reserpine stimulated the formation of sulfoconjugated noradrenaline. The efflux of noradrenaline from platelets was measured in parallel and was found to be directly related to the proportion of non metabolized to metabolized noradrenaline in the cells. Unlike tyramine, which induced a similar release of noradrenaline and 5-HT, reserpine was less effective at inducing noradrenaline release than 5-HT release. This study indicates a preferential localization of noradrenaline in the granular pool of human platelets with the existence of an extragranular sulfoconjugated pool which is increased when the granular storage of noradrenaline is impaired. Studies of noradrenaline fluxes and metabolism may be useful in the understanding of both acquired and inherited platelet storage pool defects.

Uptake and Efflux of Noradrenaline from Platelets; a Model System for Neurogenic Mechanisms in Essential Hypertension

1. The rate (k) of initial efflux of noradrenaline from platelets was determined in 63 individuals. A highly significant correlation was found between diastolic blood pressure and efflux rate. 2. When platelets are incubated in buffers with various Na+ concentrations in the range 110–170 mmol/l a higher Na+ concentration will give a faster efflux of noradrenaline for each concentration tested. 3. The value for k was determined in 41 normotensive first-degree relatives of hypertensive individuals and 21 persons with no family history of hypertension. Efflux rate of noradrenaline was significantly higher in the relatives and within this group was a subgroup with very high k values.