Potentiation of the vasospastic response to angioplasty by pretreatment with fluoxetine. A study in the atherosclerotic rabbit.

There is evidence that angioplasty-induced vasospasm is mediated by serotonin (5-hydroxytryptamine [5-HT]) release from platelets. We tested the hypothesis that pretreatment of the atherosclerotic rabbit with fluoxetine, a platelet-uptake inhibitor of 5-HT, would reduce vasospasm after balloon angioplasty. Short-term administration of fluoxetine reduced platelet 5-HT uptake to 4% of baseline. Daily administration of fluoxetine for 7 days reduced whole-blood 5-HT levels to 28% of baseline. Thus, fluoxetine inhibited platelet 5-HT uptake in this model as predicted. Contrary to our expectations and despite the substantial reduction in whole-blood 5-HT levels, pretreatment with fluoxetine for 1 week resulted in augmentation of angioplasty-induced vasospasm in atherosclerotic rabbits. Intraperitoneal administration of fluoxetine produced vasoconstriction in normal rabbits that was augmented by 5-HT and not reversed with LY53857, a specific serotonin receptor antagonist. We postulate that this new observation is probably a result of the inhibition of the clearance mechanism for serotonin, with resultant enhancement of the effect of serotonin released by the activated platelets that are deposited on the vessel wall surface at the time of angioplasty. A direct effect of fluoxetine on serotonergic receptors is a second possible mechanism for the observed effect.