Stenosis and Vascular Damage as an Experimental Model of Arterial Thrombosis: A Role for Prostanoids
Arachidonic acid, a membrane bound fatty acid, is released following a variety of stimuli. Upon release the fatty acid undergoes a series of reactions which may yield prostanoids. Prostanoids are potent agents capable of eliciting profound effects within their immediate environment. One such effect, the formation of an arterial thrombus, is regulated by the interaction of the endothelium and subendothelium of the blood vessel wall with platelets and white blood cells (de Gaetano et al., 1986; Dejana, 1987; Prosdocimi et al., 1988a). Once activated, platelets may aggregate to generate the thrombus, often formed in patients with coronary atherosclerosis. This process may, in turn, lead to an active phase of unstable angina or to a myocardial infarction (see for review Fuster et al., 1988). In addition, it has been suggested that the thrombotic procest plays a major role in provoking cerebral and peripheral ischemic pathology (Folts, 1980; Born et al., 1983; Kistler et al., 1984; Fitzgerald et al. 1984; Hess et al., 1985). Thus, the study of prostanoids in arterial thrombosis is an area of intensive investigation. This article will focus on the role of two arachidonate metabolites, prostacyclin and thromboxane, and the application of an experimental model of arterial thrombosis induced by vessel wall damage and flow alterations.
Unable to display preview. Download preview PDF.
- Ashton, J.H., Schmitz, J.M., Campbell, W.B., Ogletree, M.L., Raheja, S., Taylor, A.L., Fitzgerald, C., Buja, L.M. and Willerson, J.T., 1986, Inhibition of cyclic flow variations in stenosed canine coronary arteries by thromboxane A2/prostaglandin H2 receptor antagonists, Circulations Res, 59: 568.CrossRefGoogle Scholar
- Bertha, B.G., and Folts, J.D., 1984, Inhibition of epinephrine-exacerbated coronary thrombus formation by prostacyclin in the dog, J. Lab. Clin. Med., 103:204.Google Scholar
- Bush, L.R., Campbell, W.B., Kern, K., Tilton, G.D., Apprill, P., Ashton, J., Schmitz, J., Buja, L.M., and Willerson, J.T., 1984a, The effects of alpha2-adrenergic and serotoninergic antagonists on cyclic blood flow alterations in stenosed canine coronary arteries, Circ. Res., 55: 642.CrossRefGoogle Scholar
- Fitzgerald, D.J., Wright, F., and Fitzgerald, G.A., 1987, Platelet-dependent reocclusion following coronary thrombolysis with tissue plasminogen activator. Clin. Res., 35: 278A (Abstr.).Google Scholar
- Folts, J.D., 1980, Platelet aggregation in stenosed coronary or cerebral arteries: A mechanism for sudden death?, Wisc. Med. J., 79:24. Folts, J.D., Gallagher, K., and Rowe, G.G., 1982, Blood flow reductions in stenosed canine coronary arteries: vasospasm or platelet aggregation? Circulation, 65: 248.CrossRefGoogle Scholar
- Galli, C., Agradi, E., Petroni, A., and Socini, A., 1980,effects of 8-monochloro-3-beta-diethylaminoethyl-4-methyl-7-ethoxy carbonyl methoxy coumarin (AD6) on aggregation, arachidonic acid metabolism and thomboxane B2 formation in human platelets, Pharmacol. Res. Commun., 12: 329.Google Scholar
- Petroni, A., Socini, A., Blasevich, M., Borghi, A., Galli C., Differential effects of various vasoactive drugs on basal and stimulated levels of TXB2 and 6-ketoPGFlalpha in rat brain, Prostaglandins, 29: 579.Google Scholar
- Prosdocimi, M., Finesso, M., Gorio, A., Languino, L.R., Del Maschio, A., Castagnoli, M.N., de Gaetano, G., and Dejana, E., 1985a, Coronary and systemic 6-ketoprostaglandin Flalpha and thromboxane B2 during myocardial ischemia in dog, Am. J. Physiol., 248:H-493.Google Scholar
- Prosdocimi, M., Finesso, M., Tessari, F., Gorio, A., Languino, L.R., de Gaetano, G., and Dejana, E., 1985b, Inhibition by AD6 (8-monochloro-3-beta-diethylaminoethyl-4-methyl-7- ethoxycarbonylmethoxy coumarin) of platelet aggregation in dog stenosed coronary artery, Thromb. Res., 39: 399.CrossRefGoogle Scholar
- Prosdocimi, M., Zatta, A., and Finesso, M., Stenosis and vascular damage as a cause of thrombosis in the dog femoral artery, Naunyn-Schmiedeberg’s Arch. Pharmacol., in press.Google Scholar
- Uchida, Y., and Murao, S., 1981, Effects of thromboxane synthetase inhibitors on cyclical reduction of coronary blood flow in dogs, JPN Heart J, 22: 971.Google Scholar
- Zanetti, A., Zatta, A., Prosdocimi, M., and Dejana, E., The effect of AD6 (8-monochloro-3-beta-diethylamino-ethyl-4-methyl-7-ethoxycarbonylmethoxy coumarin) on washed human platelet aggregation induced by platelet activating factor (PAF) and epinephrine, Europ. J. Pharmacol., 128: 119.CrossRefGoogle Scholar