Studies on the antihypertensive action of L-tryptophan.

The administration of L-tryptophan to spontaneously hypertensive rats caused a dose-related decrease in blood pressure. Maximal reductions occurred 2 hr postinjection. This effect could be attenuated by 1) coadministration of valine, an amino acid that competes with tryptophan for brain uptake; 2) pretreatment with metergoline, a serotonin receptor antagonist; and 3) pretreatment with parachlorophenylalanine, which inactivates tryptophan hydroxylase. In contrast, the effect of tryptophan on blood pressure could be enhanced by pretreatment with fluoxetine, a drug which blocks serotonin reuptake into presynaptic terminals. Taken together, these results indicate that tryptophan injection lowers blood pressure by a mechanism involving increased tryptophan uptake into brain, followed by enhanced conversion of the amino acid to serotonin (not tryptamine) and, ultimately, increased release of serotonin by brain neurons. The data thus support the notion that serotonergic neurons in the rat brain function in circuits that lower blood pressure.