Response to Blood Pressure in Mutant Rats Lacking the 5-Hydroxytryptamine Transporter
We are pleased to become aware of research by Homberg et al,1 who investigated whether 5-hydroxytryptamine (5-HT) transporter (SERT) plays a role in regulating blood pressure in female SERT knockout rats. We agree with their interpretation that the absence of SERT does not exacerbate or reduce the ability of ωN-nitro-l-arginine (l-NNA) to elevate blood pressure increase in the SERT knockout (SERT−/−) female rats. In studies with mice, there are observations suggesting that other components of the serotonergic system changed compared with wild-type mice when functional SERT is removed. Investigators observed an increase of 5-HT synthesis (greater in female mice) but decrease of 5-HT tissue concentration in SERT−/− mice compared with wild-type mice.2 A downregulation of 5-HT2A/2C receptor–mediated phospholipase A2 (PLA2) signaling is reported in SERT−/− mice.3 Moreover, organic cation transporter 1 mRNA expression was found in SERT−/− mice brain (not in wild-type mice brain) and upregulated in SERT−/− mice small intestine. Organic cation transporter 1 can transport 5-HT across the membrane, which might compensate for the absence of SERT in SERT−/− mice.4 Thus, it is reasonable to suggest that there maybe adaptations of these SERT−/− rats for lifelong depletion of SERT, some of which we are not yet aware. Further study on arterial receptor expression, contraction, and local uptake/release of 5-HT in SERT−/− rats would help to characterize possible compensatory mechanisms. Moreover, additional experiments in the male rats and other forms of experimental hypertension will determine whether this conclusion can be extrapolated to hypertension in general. Nevertheless, the study by Homberg et al1 is important in that they have developed a new SERT−/− rat model and raised the issue of whether SERT is involved in blood pressure regulation both in normal and elevated states.
Homberg J, Mudde J, Braam B, Ellenbroek B, Cuppen E, Joles JA. Blood pressure in mutant rats lacking the 5-hydroxytryptamine transporter. Hypertension. 2006; 48: e115–e116.
Chen JJ, Li Z, Pan H, Murphy DL, Tamir H, Koepsell H, Gershon MD. Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter: Abnormal intestinal motility and the expression of cation transporters. J Neurosci. 2001; 21: 6348–6361.