A novel S-nitrosothiol causes prolonged and selective inhibition of platelet adhesion at sites of vascular injury.
OBJECTIVE
Platelet adhesion to areas of endothelial denudation following angioplasty is an important factor contributing to the limitations of this technique. Lipophilic S-nitrosothiols like S-nitroso-N-valerylpenicillamine (SNVP) are novel nitric oxide (NO) donor drugs with anti-platelet and vasodilator properties that are selective for areas of endothelial denudation. Here we assess the inhibitory effect of SNVP on platelet adhesion to angioplastied rabbit carotid arteries.


METHODS
A rabbit model was used to measure adhesion of radiolabelled platelets to carotid arteries following balloon angioplasty. The effects of SNVP were compared to the conventional NO donor, nitroglycerin (NTG). Electron microscopy was used to visualize adhering platelets.


RESULTS
Angioplasty resulted in endothelial denudation with only a modest reduction in vessel contractility. In vivo administration of NTG and SNVP (both 200 nmol) prevented the hyper-aggregability (approximately 20%) of circulating platelets caused by angioplasty. However, bolus NTG failed to inhibit adhesion of radiolabelled platelets 30 min after angioplasty, despite inducing a transient 30% reduction in systemic blood pressure. In contrast, equimolar SNVP had little effect on blood pressure but markedly inhibited platelet adhesion (62% compared to control; P=0.003). Platelet adhesion was confirmed with electron microscopy.


CONCLUSIONS
The prolonged effects of SNVP at sites of endothelial damage suggest that novel S-nitrosothiols might offer a means of targeted delivery of an antiplatelet agent to areas of vascular injury.
Miller
Mark R
MR
Centre for Cardiovascular Science, University of Edinburgh, UK.
Hanspal
Inderraj S
IS
Hadoke
Patrick W F
PW
Newby
David E
DE
Rossi
Adriano G
AG
Webb
David J
DJ
Megson
Ian L
IL
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D001792:Blood Platelets / Q000648:ultrastructure; D001794:Blood Pressure / Q000187:drug effects; D020212:Carotid Artery Injuries / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D017536:Carotid Artery, Common / Q000503:physiopathology / Q000648:ultrastructure; D008297:Male; D008855:Microscopy, Electron, Scanning; D005996:Nitroglycerin / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; C473423:S-nitroso-N-valerylpenicillamine; D014665:Vasodilator Agents; D005996:Nitroglycerin; D010396:Penicillamine