thromboplastin and imidapril

Reduced activity of endothelial nitric oxide (NO) may be involved in thrombus formation on atherosclerotic plaques, a major cause of acute coronary syndrome. However, mechanisms of such increase in arterial thrombogenecity have not been fully understood. We previously reported that long-term inhibition of NO synthesis by administration of N(G)-nitro-L-arginine methyl ester (L-NAME) causes hypertension and activates vascular tissue angiotensin-converting enzyme (ACE) activity. We used this model to investigate the mechanism by which long-term impairment of NO activity increases arterial thrombogenecity. We observed cyclic flow variations (CFVs), a reliable marker of platelet thrombi, after the production of stenosis of the carotid artery in rats treated with L-NAME for 4 wk. The thrombin antagonist argatroban suppressed the CFVs. The CFVs were detected in rats receiving L-NAME plus hydralazine but not in rats receiving L-NAME plus an ACE inhibitor (imidapril). Treatment with the ACE inhibitor imidapril, but not with hydralazine, prevented L-NAME-induced increases in carotid arterial ACE activity and attenuated tissue factor expression. These results suggest that long-term inhibition of endothelial NO synthesis may increase arterial thrombogenecity at least in part through angiotensin II-induced induction of tissue factor and the resultant thrombin generation. These data provide a new insight as to how endothelial NO exhibits antithrombogenic properties of the endothelium.

Topics: Administration, Oral; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Antithrombins; Arginine; Blood Flow Velocity; Blood Pressure; Carotid Arteries; Carotid Artery Thrombosis; Enzyme Inhibitors; Gene Expression Regulation; Heart Rate; Imidazoles; Imidazolidines; Injections, Intravenous; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Peptidyl-Dipeptidase A; Pipecolic Acids; Platelet Aggregation; Prothrombin Time; Rats; Rats, Inbred WKY; Sulfonamides; Thromboplastin; Transcription, Genetic