Inhaled NO inhibits platelet aggregation and elevates plasma but not intraplatelet cGMP in healthy human volunteers.
Effects of inhaled nitric oxide (NO) on human platelet function are controversial. It is uncertain whether intraplatelet cGMP mediates the effect of inhaled NO on platelet function. We investigated the effect of 30 ppm inhaled NO on platelet aggregation and plasma and intraplatelet cGMP in 12 subjects. We performed platelet aggregation studies by using a photooptical aggregometer and five agonists (ADP, collagen, epinephrine, arachidonic acid, and ristocetin). During inhalation, the maximal extent of platelet aggregation decreased by 75% with epinephrine (P < 0.005), 56% with collagen (P < 0.005), and 20% with arachidonic acid (P < 0.05). Responses to ADP (8% P > 0.05) and ristocetin (5% P > 0.05) were unaffected. Platelet aggregation velocity decreased by 64% with collagen (P < 0.005), 60% with epinephrine (P < 0.05), 33% with arachidonic acid (P < 0.05), and 14% with ADP (P > 0.05). Plasma cGMP levels increased from 2.58 +/- 0.43 to 9.99 +/- 5.57 pmol/ml (P < 0.005), intraplatelet cGMP levels were unchanged (means +/- SD: 1.96 +/- 0.58 vs. 2.71 +/- 1.67 pmol/109 platelets; P > 0.05). Inhaled NO inhibits platelet aggregation via a cGMP independent mechanism.
Division of Cardiology, Department of Critical Care Medicine, Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario, Canada M5J 1X8.
Maurice
M
Beghetti
Catherine
C
Sparling
Peter N
PN
Cox
Derek
D
Stephens
Ian
I
Adatia
D000280:Administration, Inhalation; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D006152:Cyclic GMP / Q000097:blood*; D005260:Female; D006454:Hemoglobins; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000008:administration & dosage*; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count
D006454:Hemoglobins; D009569:Nitric Oxide; D006152:Cyclic GMP