Serotonin-induced blood flow changes in the rat hindlegs after unilateral ligation of the femoral artery. Inhibition by the S2 receptor antagonist ketanserin.

Collateral arteries can clearly be visualized in corrosion cast material after ligation of the femoral artery in rats. To characterize the influence of serotonin on the blood circulation under the experimental condition of unilateral ligation, we performed intermuscular thermoflow measurements. The data showed that intraperitoneal serotonin (8.7 and 20 mg.kg-1) injection markedly reduced the muscle temperature in both hindlegs. However, the effect was significantly more pronounced on the ligated side, where the blood was supplied through a collateral circulation, than on the non-ligated side with its normal arterial vasculature. Almost identical changes were obtained in rats with an early as well as in animals with a more advanced stage of collateral development (challenge with 8.7 mg.kg-1 serotonin). Evans blue dye experiments and angiographic data further revealed that, after challenge with 20 mg.kg-1 serotonin, the severe temperature decrease at the ligated side probably reflected a nearly complete blockage of blood supply. Pretreatment with the S2 receptor antagonist ketanserin (2.5 mg.kg-1) resulted in a significant reduction in the extent and duration of the serotonin-induced temperature decrease as revealed by the temperature measurements; such a treatment inhibited also the blockage in blood flow as seen with the other techniques. This study shows that serotonin, through its vasoconstrictive properties, can restrict the blood flow to the lower extremities of the rat, particularly when the blood is supplied through collateral circulation. This probably results in moderate to severe skeletal muscle ischaemia. It also suggests that the vasoconstriction is not only important in the inhibition of collateral blood flow in recently established collaterals but also in collateral vessels in a more advanced stage of development. The in vivo vasoconstriction and subsequent reduction of the blood supply caused by serotonin can be effectively counteracted by pretreatment with ketanserin.