ALPHA-ADRENOCEPTOR BLOCKADE BY PHENTOLAMINE INHIBITS ADRENALINE-INDUCED PLATELET ACTIVATION INVIVO WITHOUT AFFECTING RESTING MEASUREMENTS

1. The effects of phentolamine (500-mu-g/min) on platelet aggregability in vivo at rest and during adrenaline infusion were assessed by ex vivo filtragometry and measurements of plasma beta-thromboglobulin levels in 10 healthy male subjects. Plasma levels of von Willebrand factor antigen and free fatty acids were also measured. 2. Adrenaline induced marked and expected increases in heart rate and systolic blood pressure and decreased diastolic blood pressure when venous plasma adrenaline levels were elevated from 0.12 +/- 0.02 to 2.9 +/- 0.3 nmol/l (P < 0.01). 3. Adrenaline caused platelet activation in vivo. Ex vivo filtragometry readings were shortened by 58 +/- 9% (P < 0.01), plasma beta-thromboglobulin levels increased by 99 +/- 44% (P < 0.01) and platelet counts increased by 26 +/- 6% (P < 0.01). Plasma levels of von Willebrand factor antigen and free fatty acids increased by 53 +/- 5% and 475 +/- 113% (both P < 0.01), respectively. 4. Phentolamine enhanced the beta-adrenergic vasodilator responses to adrenaline, as both the decrease in diastolic blood pressure and the reflexogenic increase in heart rate were enhanced (both P < 0.01). Marked elevations in plasma noradrenaline levels were found during infusions of phentolamine and adrenaline (P < 0.001). 5. Phentolamine did not alter platelet indices at rest, but abolished adrenaline-induced platelet activation, as filtragometry readings, plasma beta-thromboglobulin levels and platelet counts remained at, or below, resting levels. Responses of plasma levels of von Willebrand factor antigen and free fatty acids to adrenaline were not influenced by phentolamine and did not seem to influence platelet responses. 6. Thus, platelet activation by adrenaline in vivo is mediated via alpha-adrenoceptors, apparently with minor influences of other physiological responses. Circulating and/or locally released catecholamines may activate platelets directly via alpha-adrenoceptor stimulation during stressful physiological and pathophysiological conditions in humans.