Elevated plasma concentration of NO and cGMP may be responsible for the decreased platelet aggregation and platelet leukocyte conjugation in platelets hypo-responsive to catecholamines

Impaired responsiveness to epinephrine and other catecholamines (CA) were previously reported in platelets of 20 similar to 30% healthy Japanese and Koreans. In the present study, the possible mechanisms of different responsiveness to CA in platelets of CA hypo-responders (CA-HY) and CA good-responders (CA-GR) were investigated. Increased platelet-leukocyte conjugate (PLC) formations were observed with whole blood of CA-GR than with that of CA-HY in both non-stimulated [mean fluorescence intensity (MFI) values: 1.33 +/- 0.26 vs. 1.16 +/- 0.19] and ADP (MFI: 5.54 +/- 3.46 vs. 2.15 +/- 1.13) or TRAP (MFI: 5.11 +/- 2.32 vs. 3.38 +/- 1.47) activated states. The platelets of CA-GR, when stimulated with ADP (10 mu M), released approximately twice the amount of ATP than those of CA-HY (0.88 +/- 0.65 and 0.45 +/- 0.36 nmole, respectively). Nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels were significantly higher in non-stimulated PRP of CA-HY than in that of CA-GR (70.3 +/- 24.1 mu M and 14.1 +/- 4.9 nM vs. 41.1 +/- 15.8 mu M and 6.7 +/- 2.4 nM, respectively). The platelet-monocyte conjugation induced with either ADP or TRAP was significantly reduced in CA-GR with the addition of linsidomine, a NO donor, (MFI: 2.78 +/- 0.43 vs. 3.73 +/- 0.90, or 4.28 +/- 0.95 vs. 5.76 +/- 1.33, respectively). Moreover, the degree of platelet aggregation and the ATP secretion induced by epinephrine in CA-GR were significantly retarded with the addition of either linsidomine or 8-Bromo-cGMP (a cGMP analog) with more substantial effects on ATP release than aggregation. The results suggested that elevated NO and/or cGMP plasma levels may be responsible for the lower platelet aggregation and PLC formation observed in CA-HY than that in CA-GR.