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Nitroglycerin‐inhibited whole blood aggregation is partially mediated by calcitonin gene‐related peptide–a neurogenic mechanism
Author(s) -
Booth Brian P.,
Nolan Timothy D.,
Fung HoLeung
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701408
Subject(s) - calcitonin gene related peptide , calcitonin , chemistry , platelet , endocrinology , medicine , nitric oxide , nitric oxide synthase , incubation , mechanism of action , neuropeptide , pharmacology , platelet activation , in vitro , biochemistry , receptor
1 The role of the vasculature and calcitonin gene‐related peptide (CGRP) in nitroglycerin (NTG)‐mediated platelet inhibition was studied. 2 In vitro incubations of CGRP in whole blood induced a dose‐dependent inhibition of platelet aggregation with an IC 50 of 62.1 n M . 3 The platelet inhibition induced by CGRP was blocked by co‐incubation of 0.53 μ M CGRP 8‐37 , as well as 30 μ M N G ‐nitro‐monomethyl‐ L ‐arginine ( L ‐NMMA). 4 In a separate group of experiments, 100 n M NTG in rat whole blood (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 platelet inhibition to 31.6±6.8% ( P <0.01). Incubation of WB and AT with 30 μ M L ‐NMMA reduced NTG‐induced inhibition of platelet aggregation to 26.4±4.2% ( P <0.001). 5 It is concluded that vascular tissue contributes to the antiplatelet mechanism of action of NTG. Furthermore, NTG apparently evokes the release of CGRP from vascular tissue and this neuropeptide contributes to the antiplatelet actions of NTG. 6 The antiplatelet activity of CGRP in whole blood is mediated primarily through the activation of nitric oxide synthase.British Journal of Pharmacology (1997) 122 , 577–583; doi: 10.1038/sj.bjp.0701408