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 µg/kg/min), a stimulator of soluble guanylate cyclase, significantly attenuated the adherence of platelets to the injured carotid arteries. In comparison, infusion of milrinone, acAMP 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.

Signal transduction by cGMP-dependent protein kinases and their emerging roles in the regulation of cell adhesion and gene expression

“…1992). These in vitro results were confirmed using an in vivo rat carotid artery model system (Vemulapalli et al 1996). Newly developed direct activators/modulators of GCs like YC-1 may therefore be powerful inhibitors of both initial and long-term platelet adhesion to collagen, and their inhibitory effect may even be potentiated by selective inhibitors of cGMP-specific phosphodiesterases such as dipyridamole (Wu etal.…”

Sildenafil Improves Coronary Artery Patency in a Canine Model of Platelet-Mediated Cyclic Coronary Occlusion After Thrombolysis

“…The PDE5 inhibitors have been shown to reduce platelet aggregation in an animal model of endothelial injury (28), and reduce human ex vivo platelet aggregability (29). PDE5 inhibitors also augment the ability of NO-donor compounds to decrease platelet aggregation in vitro (17) and platelet-mediated thrombosis in vivo (29).…”

Sexual activity as a trigger for intracranial hemorrhage

“…Two (12.5 %) patients in the current series reported use of oral PDE-5 inhibitors and both were associated with sexual activity. While PDE-5 inhibitors do not carry a warning specific to ICH, animal model and ex vivo data suggest that PDE-5 inhibitors can inhibit platelet aggregation [6,10,41]. Other side effects, including headache and flushing [16,27], indicate that the vascular effects may not be limited to the corpus cavernosum of the penis.…”