Hypertension and tachycardia produced by inhibition of reuptake of 5-hydroxytryptamine by fluoxetine in the rat.

In rats anaesthetized with urethane, increasing the activity of 5-hydroxytryptamine receptors or the level of cuntional serotonin in the brain with the inhibitors of the reuptake of serotonin, fluoxetine, produced both hypertension and tachycardia. The hypertension induced by fluoxetine was significantly inhibited by pretreatment of the animals with ketanserin (a serotonin receptor antagonist), by bilateral vagotomy, spinal transection or bilateral adrenalectomy. On the other hand, the tachycardia induced by fluoxetine was significantly inhibited by pretreatment with ketanserin or bilateral vagotomy, but not by spinal transection or adrenalectomy. The data indicate that fluoxetine acts through serotonin receptors in the central nervous system by influencing autonomic outflow to induce both hypertension and tachycardia.