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Am J Physiol Heart Circ Physiol (May 15, 2003). doi:10.1152/ajpheart.00622.2002
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Submitted on July 19, 2002
Accepted on May 2, 2003

Inhaled nitric oxide inhibits platelet aggregation and elevates plasma but not intraplatelet cGMP in healthy human volunteers

Maurice Beghetti1, Catherine Sparling2, Peter N. Cox3, Derek Stephens4, and Ian Adatia5*

1 Division of Cardiology, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada
2 Division of Hematology, Hospital for Sick Children, Toronto, Ontario, Canada
3 Department of Critical Care Medicine, Hospital for Sick Children, Toronto, Ontario, Canada
4 Department of Population Health Sciences, Hospital for Sick Children, Toronto, Ontario, Canada
5 Division of Cardiology, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Critical Care Medicine, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada

* To whom correspondence should be addressed. E-mail: ian.adatia{at}sickkids.ca.

The effects of inhaled nitric oxide on human platelet function are controversial. It is uncertain if intraplatelet cGMP mediates the effect of inhaled NO on platelet function. We investigated the effect of 30 ppm inhaled nitric oxide on platelet aggregation and both plasma and intraplatelet cGMP in 12 subjects. We performed platelet aggregation studies using a photo-optical aggregometer and 5 agonists (ADP, collagen, epinephrine, arachidonic acid and ristocetin). During inhalation, maximal extent of platelet aggregation decreased by 75% with epinephrine (P < 0.005), 56% with collagen (P <0.005), 20% with arachidonic acid (P < 0.05). The 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 (mean ± sd 1.96± 0.58 versus 2.71±1.67 pmol/ 109 platelets P>0.05). Inhaled nitric oxide inhibits platelet aggregation via a cGMP independent mechanism.




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