Nitroglycerin-inhibited whole blood aggregation is partially mediated by calcitonin gene-related peptide -- a neurogenic mechanism.
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 IC50 of 62.1 nM. 3. The platelet inhibition induced by CGRP was blocked by co-incubation of 0.53 microM CGRP8-37, as well as 30 microM N(G)-nitro-monomethyl-L-arginine (L-NMMA). 4. In a separate group of experiments, 100 nM 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 CGRP8-37 with NTG and AT in WB reduced platelet inhibition to 31.6+6.8% (P<0.01). Incubation of WB and AT with 30 microM 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.
Booth
B P
BP
Department of Pharmaceutics, State University of New York at Buffalo, 14260, U.S.A.
Nolan
T D
TD
Fung
H L
HL
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D017097:Electric Impedance; D066298:In Vitro Techniques; D008297:Male; D018377:Neurotransmitter Agents / Q000502:physiology*; D005996:Nitroglycerin / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019323:omega-N-Methylarginine / Q000494:pharmacology
D018377:Neurotransmitter Agents; D010975:Platelet Aggregation Inhibitors; D019323:omega-N-Methylarginine; D000244:Adenosine Diphosphate; D005996:Nitroglycerin; D015740:Calcitonin Gene-Related Peptide