Vasopressin acts on platelets to generate procoagulant activity.
The aim of our study was to examine whether arginine vasopressin (AVP) is able to evoke in human platelets a procoagulant response due to activation of an Na+/H+ exchanger. It was found that treatment of platelets with AVP (20-100 nmol/l) results in generation of a weak calcium signal, activation of Na+/H+ exchanger, aggregation, and development of a procoagulant response. The AVP-evoked procoagulant response was dose and time dependent, weaker than that produced by collagen or monensin (mimics Na+/H+ exchanger), and less pronounced following the inhibition of Na+/H+ exchanger by 5-(N-ethyl-N-isopropyl) amiloride or genistein. Flow cytometry studies reveal that in-vitro platelet treatment with AVP results in an unimodal left shift in the forward and side scatter of the entire platelet population, indicating morphological changes on the plasma membrane. The shift was dose related, weaker than that evoked by collagen, similar to that produced by monensin and strongly reduced in the presence of 5-(N-ethyl-N-isopropyl) amiloride or genistein. Using flow cytometry, we demonstrated enhanced expression of phosphatidylserine on the AVP-treated platelets. AVP-evoked phosphatidylserine exposure was dose dependent, inhibited by 5-(N-ethyl-N-isopropyl) amiloride or genistein and weaker than that produced by collagen. AVP in a dose-dependent manner produced a rise in platelet volume. The swelling was inhibited by 5-(N-ethyl-N-isopropyl) amiloride, and its kinetics was similar to that observed in the presence of monensin. We conclude that prolonged treatment of platelets with AVP results in a procoagulant response, which may occur as a consequence of Na+ influx mediated by Na+/H+ exchanger.
Tomasiak
Marian
M
Department of Physical Chemistry, Medical University of Bialystok, KIlinskiego 1, Bialystok, Poland. mtomask@amb.edu.pl
Stelmach
Halina
H
Rusak
Tomasz
T
Ciborowski
Michał
M
Radziwon
Piotr
P
D000584:Amiloride / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D005434:Flow Cytometry; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D010718:Phosphatidylserines / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count; D017670:Sodium Compounds / Q000097:blood; D017923:Sodium-Hydrogen Exchangers / Q000097:blood
D010718:Phosphatidylserines; D017670:Sodium Compounds; D017923:Sodium-Hydrogen Exchangers; D001127:Arginine Vasopressin; D000584:Amiloride; D019833:Genistein