IMPLICATIONS OF THROMBOSIS AND VASOSPASM IN PERIPHERAL VASCULAR-DISEASE

Platelet activation releases not only thromboxane A2 but also serotonin, another vasoconstrictor agent that acts on blood vessels through a specific, 5-HT2 receptor. The development of ketanserin, the selective 5-HT2-receptor blocker, has made it possible to explore the role of serotonin in animal models and patients with endothelial injury and atherosclerotic disease. In animal models, growing collateral arterial vessels are exquisitely sensitive to the vasoconstrictor effects of serotonin, which are reversed by ketanserin. When endogenous platelet activation is induced by endothelial injury, a combination of ketanserin and a thromboxane synthesis inhibitor or antagonist is more effective at reversing collateral arterial vasoconstriction than either agent alone. More recently, studies at the time of angiography in humans with advanced atherosclerosis have shown that more than 50% display a dilator response to ketanserin in low doses: the response primarily involves dilatation of collateral arterial vessels. which is associated with a significant increase in calf blood flow. These findings support existing evidence that platelet products contribute to the ischemia syndromes due to atherosclerosis. and provide a promising approach to improved management.