Contribution of vascular tissue to the antiplatelet activity of sodium nitroprusside

We tested whether or not platelet inhibition by sodium nitroprusside (SNP) was enhanced by vascular tissue production of nitric oxide (NO) and calcitonin gene-related peptide (CGRP) release. Platelet aggregation was determined with whole blood impedance aggregometry after incubations of SNP in the presence or absence of rat aortic tissue (AT) or AT + CGRPS_8-37 (a specific CGRP antagonist). SNP alone had no effect on platelet aggregation until 100 μM was used (2.3 + 1.5 Ω vs. control aggregation of 9.9 ± 2.0 Ω; p < 0.001). Co-incubation of AT with SNP significantly enhanced platelet inhibition at 1 (1.6 ± 1.3 Ω p <0.001), 10 (0.7 ± 0.4 Ω; p < 0.001), and 100 μM (0. 3 ± 0.3 Ω; p < 0.001). CGRP(8.37) did not significantly antagonize aggregation by SNP + AT (p > 0.05). The inhibition of platelet aggregation by 10 μM SNP was inhibited by methylene blue (MB) (9.0 ± 1.7 Ω at 10 μM; 11.7 ± 2.4 Ω at 100 μM; p < 0.001) but not by 30 μM L-Nυ- monomethyl-L-arginine (L-NMMA; 2.9 ± 1.8 Ω; p > 0.05). These results indicate that vascular tissue significantly contributes to the ability of SNP to inhibit platelet aggregation, probably through greater vascular enzymatic production of NO, but not by releasing CGRR in contrast to nitroglycerin.