Prostacyclin and thromboxane A₂ formation in response to adrenergic stimulation in humans: A mechanism for local control of vascular response to sympathetic activation?

Summary: Prostacyclin (PGI₂) and thromboxane A₂ (TxA₂), antiaggregating and aggregating agents, may be involved in the control of local vasomotor tone owing to their vasoactive properties. In 15 healthy young volunteers, circulating PGI₂ (biological assay using superfusion technique) and plasma TxA₂ levels (measured by radioimmunoassay as its stable derivative TxB₂) have been investigated. Adrenergic stimulation was induced by a 2 min cold application and its effectiveness was checked in all subjects by the changes in forearm calculated vascular resistance (blood flow was measured by strain gauge plethysmography), and in six subjects by changes in catecholamine plasma levels (radioenzymatic assay). Cold application induced a sharp increase in calculated vascular resistance and plasma noradrenaline concentration in all subjects. Adrenergic stimulation was associated with a prompt elevation of circulating PGI₂ (from 6.67 ± 2.38 to 12.18 ± 2.95 ng·cm^-3, P <0.001) and TxB₂ levels (from 0.49 ± 0.18 to 1.10 ± 0.61 pmol·cm^-3, P <0.001). PGI₂ and TxB₂ increases disappeared within 10 min. In subjects treated with 5 mg·kg^-1 ASA, both TxB₂ resting levels and their increase after adrenergic stimulation were not significantly different from values before ASA although platelets were unable to produce TxB₂. Therefore, platelets were not the source of TxB₂ in plasma. After 10 mg·kg^-1 ASA, TxB₂ increase following adrenergic stimulation was unaffected whereas PGI₂ elevation was completely blocked and the increase in calculated vascular resistance was significantly higher than in subjects pretreated with saline. These findings indicate that TxB₂ and PGI₂ formation may represent a modulating mechanism of vascular response to adrenergic stimulation.