NITROGLYCERIN-INHIBITED WHOLE-BLOOD AGGREGATION IS PARTIALLY MEDIATEDBY CALCITONIN-GENE-RELATED PEPTIDE - A NEUROGENIC MECHANISM

1 The role of the vasculature and calcitonin gene-related peptide (CGR P) in nitroglycerin (NTG)mediated platelet inhibition was studied. 2 I n vitro incubations of CGRP in whole blood induced a dose-dependent in hibition of platelet aggregation with an IC50 of 62.1 nM. 3 The platel et inhibition induced by CGRP was blocked by co-incubation of 0.53 mu M CGRP(8-37), as well as 30 mu M N-G-nitro-monomethyl-L-arginine (L-NM MA).4 In a separate group of experiments, 100 nM NTG in rat whole bloo d (WB) induced platelet inhibition of 6.0+/-1.3% (mean+/-s.d.), which was enhanced to 77.6+/-3.5% by the addition of rat aortic tissue (AT) (P<0.001). The inclusion of CGRP(8-37) with NTG and AT in WB reduced p latelet inhibition to 31.6+/-6.8% (P<0.01). Incubation of WB and AT wi th 30 mu M L-NMMA reduced NTG-induced inhibition of platelet aggregati on to 26.4+/-4.2% (P<0.001). 5 It is concluded that vascular tissue co ntributes to the antiplatelet mechanism of action of NTG. Furthermore, NTG apparently evokes the release of CGRP from vascular tissue and th is neuropeptide contributes to the antiplatelet actions of NTG. 6 The antiplatelet activity of CGRP in whale blood is mediated primarily thr ough the activation of nitric oxide synthase.