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 microM was used (2.3 + 1.5 omega vs. control aggregation of 9.9 +/- 2.0 omega; p < 0.001). Co-incubation of AT with SNP significantly enhanced platelet inhibition at 1 (1.6 +/- 1.3 omega; p < 0.001), 10 (0.7 +/- 0.4 omega; p < 0.001), and 100 microM (0.3 +/- 0.3 omega; p < 0.001). CGRP(8-37) did not significantly antagonize aggregation by SNP + AT (p > 0.05). The inhibition of platelet aggregation by 10 microM SNP was inhibited by methylene blue (MB) (9.0 +/- 1.7 omega at 10 microM; 11.7 +/- 2.4 omega at 100 microM; p < 0.001) but not by 30 microM L-N(upsilon)-monomethyl-L-arginine (L-NMMA; 2.9 +/- 1.8 omega; 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 CGRP, in contrast to nitroglycerin.
Booth
B P
BP
Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, 14260, USA.
Fung
H L
HL
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D015740:Calcitonin Gene-Related Peptide; D008751:Methylene Blue