Effect of neuronal uptake blockade on the amplifying effect of serotonin on sympathetic vasoconstriction in rat autoperfused hindlimb

Abstract

The effects of serotonin on resting perfusion pressure and on vasoconstrictor responses to electrical stimulation of the lumbar sympathetic outflow were investigated in the autoperfused hindlimb of the pithed rat. beta-Adrenoceptors, muscarinic cholinoceptors, and angiotensin converting enzyme were blocked. Infusion of serotonin (100 ng/min i.a. for 10 min) produced variable increases in hindlimb perfusion pressure of up to 100 mm Hg. During infusion of serotonin, responses to spinal stimulation at 3 Hz for 20 s were decreased, whereas responses at 10 Hz for 10 s were unaffected. Within 5 min of termination of infusion, the direct vasoconstrictor effect of serotonin disappeared, whereas responses to stimulation at both 3 and 10 Hz increased significantly to around 160% of control preinfusion values. In the presence of desipramine (0.1 mg/kg, i.v.), responses to stimulation at 3 Hz were increased; during serotonin infusion the responses were unchanged (i.e., the inhibitory effect observed in the absence of desipramine did not occur), whereas after termination of infusion the responses were again significantly increased. It is concluded that in the rat autoperfused hindlimb, serotonin produces both inhibitory and facilitatory, or amplifying, effects on sympathetic vasoconstrictor responses; increasing the stimulation frequency and neuronal uptake blockade appear to favor the amplifying effect of serotonin.