Platelet alpha 2 adrenoceptor characteristics during the morning increase in platelet aggregability.
The incidence of myocardial infarction and sudden cardiac death increases in the morning, as do platelet aggregability and sympathetic activity. We considered the possibility that increased platelet aggregability in the morning was due to an increase in platelet alpha 2 adrenergic receptor number or agonist binding affinity, or to a temporal disparity between the increase in sympathetic activity that accompanies arising and the anticipated decrease in platelet high affinity alpha 2 adrenoceptors. To evaluate these possibilities, we studied eight healthy male volunteers (20-35 years) before and 1-1.5 and 3-4 h after they arose at 08.00 h and performed routine morning activities. Platelet aggregability was determined in platelet-rich plasma; alpha 2 adrenoceptor density and agonist binding affinity were determined in intact platelets and in membrane preparations using the alpha 2 selective ligand [3H]-yohimbine. The threshold concentration of epinephrine required to produce biphasic aggregation decreased (i.e. platelet aggregability increased) from 3.6 +/- 1.2 to 0.9 +/- 0.3 microM (P less than 0.05) after arising. However, alpha 2 adrenoceptor density (380 +/- 71 to 365 +/- 51 sites per platelet) and agonist binding affinity assessed simultaneously did not change after arising, suggesting that the increase in platelet aggregability is due to factors extrinsic to the platelets or to an intra-platelet mechanism distal to the receptor level.
Willich
S N
SN
Institute for Prevention of Cardiovascular Disease, Deaconess Hospital, Boston.
Tofler
G H
GH
Brezinski
D A
DA
Schafer
A I
AI
Muller
J E
JE
Michel
T
T
Colucci
W S
WS
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D004837:Epinephrine / Q000097:blood / Q000494:pharmacology; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000493:pharmacokinetics
D011941:Receptors, Adrenergic; D015016:Yohimbine; D000244:Adenosine Diphosphate; D009638:Norepinephrine; D004837:Epinephrine