title: In vivo inhibition of platelet adhesion by a cGMP-mediated mechanism in balloon catheter injured rat carotid artery.
abstract: The role of cyclic guanosine monophosphate (cGMP) versus cyclic adenosine monophosphate (cAMP) mediated mechanism in modulating platelet adhesion was investigated in balloon catheter injured rat carotid arteries. Vascular injury with balloon angioplasty significantly increased the adherence of platelets to the injured carotid arteries. Intravenous infusion of zaprinast (1 mg/kg/min), a cGMP phosphodiesterase inhibitor, or sodium nitroprusside (8 micrograms/kg/min), a stimulator of soluble guanylate cyclase, significantly attenuated the adherence of platelets to the injured carotid arteries. In comparison, infusion of milrinone, a cAMP phosphodiesterase inhibitor, or 8-bromo-cAMP failed to affect the platelet deposition in the injured carotid arteries. Nifedipine or aspirin also failed to attenuate the adherence of platelets to the injured carotid arteries. In conclusion, agents known to elevate intracellular platelet cGMP but not cAMP appear to afford the most effective protection in vivo against the adhesion of platelets to the vessel wall without intact endothelium.
authors.affiliation: Schering-Plough Research Institute, Kenilworth, N.J. 07033, USA.
authors.forename: S
authors.initials: S
authors.lastname: Vemulapalli
authors.forename: P J
authors.initials: PJ
authors.lastname: Chiu
authors.forename: S
authors.initials: S
authors.lastname: Kurowski
authors.forename: A
authors.initials: A
authors.lastname: Brown
authors.forename: B D
authors.initials: BD
authors.lastname: Hartman
authors.forename: M W
authors.initials: MW
authors.lastname: Leach
mesh_terms: D000818:Animals; D002340:Carotid Artery Diseases / Q000209:etiology* / Q000503:physiopathology; D002404:Catheterization / Q000009:adverse effects*; D008297:Male; D020105:Milrinone; D009599:Nitroprusside / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011688:Purinones / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology; D051381:Rats
chemical_list: D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; D011688:Purinones; D011728:Pyridones; D009599:Nitroprusside; C011145:zaprinast; D020105:Milrinone