The effect of naftidrofuryl, a 5-HT2 antagonist, on collateral vascular responses to serotonin and to platelet activation.

Collateral arterial supersensitivity to serotonin has been attributed to a 5-HT2 receptor mechanism because of the effectiveness of ketanserin in reversing that vasoconstrictor response. To assess that hypothesis we employed a chemically unrelated agent, naftidrofuryl, and assessed the responses of the collateral arterial supply 2 weeks after superficial femoral artery ligation to serotonin or to platelet activation induced by endothelial injury in 25 rabbits. Naftidrofuryl was effective in reversing serotonin-induced vasoconstriction in doses ranging from 0.3 to 3.0 micrograms/kg/min. Higher doses reduced blood pressure sufficiently that collateral arterial attenuation ensued. When collateral arterial vasoconstriction was induced by endothelial injury, naftidrofuryl in doses of 1.0 and 3.0 micrograms/kg/min reversed the attenuation (p < 0.001) in a dose-dependent fashion. In the absence of vasoconstriction induced by serotonin or platelet activation, naftidrofuryl in these doses did not produce vasodilatation, suggesting that the agent acted as a blocker rather than as a direct vasodilator. The observations strengthen the hypothesis that supersensitivity of collateral arterial vessels to serotonin reflects a 5-HT2 receptor mechanism.