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Serotonin (5-hydroxytryptamine; 5-HT) is a potent constrictor of isolated blood vessels. However, recent studies demonstrate that chronic 5-HT infusion results in a prolonged fall in blood pressure in the rat. This finding highlights the need for further study of 5-HT in the cardiovascular system. We tested the hypothesis that a functional serotonin transporter (SERT) is critical to enabling a 5-HT-induced fall in blood pressure. Experiments were performed in male and female rats to determine whether gender significantly affected the ability of 5-HT to lower blood pressure and to determine whether SERT dependence was different in male vs. female rats. 5-HT (25 μg/kg/min; s.c.) was infused for 7 days to male and female, SERT wild-type (WT) and SERT knockout (KO) rats. Mean arterial pressure (MAP) and heart rate were monitored via radiotelemetry. 5-HT produced a significantly greater fall in MAP (at the nadir) in the male SERT WT rat (-20 ± 1 mmHg) compared to the male SERT KO rat (-10 ± 2 mmHg). Similarly, 5-HT also produced a significantly greater fall in MAP (at the nadir) in the female SERT WT rat (-19 ± 1 mmHg) compared to the female SERT KO rat (-15 ± 0.4 mmHg). While the lack of a functional SERT protein did not prevent a 5-HT-induced fall in blood pressure, it did reduce the ability of 5-HT to lower blood pressure in the male and female SERT rat, suggesting a potentially important role for SERT in producing a 5-HT-induced fall in blood pressure.

Lack of the serotonin transporter (SERT) reduces the ability of 5-hydroxytryptamine to lower blood pressure