Alpha-adrenoceptor blockade by phentolamine inhibits adrenaline-induced platelet activation in vivo without affecting resting measurements.
1. The effects of phentolamine (500 micrograms/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 less than 0.01). 3. Adrenaline caused platelet activation in vivo. Ex vivo filtragometry readings were shortened by 58 +/- 9% (P less than 0.01), plasma beta-thromboglobulin levels increased by 99 +/- 44% (P less than 0.01) and platelet counts increased by 26 +/- 6% (P less than 0.01). Plasma levels of von Willebrand factor antigen and free fatty acids increased by 53 +/- 5% and 475 +/- 113% (both P less than 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 less than 0.01). Marked elevations in plasma noradrenaline levels were found during infusions of phentolamine and adrenaline (P less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Larsson
P T
PT
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Wallén
N H
NH
Egberg
N
N
Hjemdahl
P
P
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004837:Epinephrine / Q000037:antagonists & inhibitors* / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010646:Phentolamine / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010976:Platelet Count / Q000187:drug effects; D013997:Time Factors; D001620:beta-Thromboglobulin / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D005230:Fatty Acids, Nonesterified; D010975:Platelet Aggregation Inhibitors; D001620:beta-Thromboglobulin; D014841:von Willebrand Factor; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine