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This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/H1745    most recent ajpheart.91415.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Linder, A. E. Articles by Watts, S. W. Search for Related Content PubMed PubMed Citation Articles by Linder, A. E. Articles by Watts, S. W.

Vascular reactivity, 5-HT uptake, and blood pressure in the serotonin transporter knockout rat

Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan

Submitted 7 December 2007 ; accepted in final form 6 February 2008

The handling of serotonin [5-hydroxytryptamine (5-HT)] depends on the serotonin transporter (SERT). A SERT knockout (KO) rat is a useful model to test the hypothesis that SERT is the primary mechanism for arterial 5-HT uptake and to investigate the impact of SERT removal on blood pressure. Wild-type (WT) and KO rats were used to measure 5-HT content (plasma, raphe, aorta, carotid, and mesenteric artery), aortic isometric contraction, and blood pressure. HPLC supported the lack of circulating 5-HT in plasma (ng/ml plasma, WT, 310 ± 96; and KO, 1.0 ± 0.5; P < 0.05). Immunohistochemistry and Western blot analyses validated the presence of the SERT protein in the WT rats and a lesser expression in the KO rat. The aorta isolated from KO rats had a normal contraction to phenylephrine and norepinephrine and a normal relaxation to the endothelium-dependent agonist acetylcholine compared with the aorta from WT. In contrast, the potency of 5-HT was increased in the aorta from KO rats compared with WT rats [–log EC₅₀ (M); WT, 5.71 ± 0.08; and KO, 6.7 ± 0.18] and maximum contraction was reduced [%phenylephrine (10 µM) contraction, WT, 113 ± 6%; and KO, 52 ± 12%]. 5-HT uptake was reduced but not abolished in arteries of the KO compared with the WT rats. Diurnal mean arterial blood pressure, heart rate, and locomotor activity level of the KO rats were similar to the WT rats. These data suggest that there are other mechanisms of 5-HT uptake in the arteries of the rat and that although the absence of circulating 5-HT and/or SERT function sensitizes arteries to 5-HT, SERT dysfunction does not impair normal blood pressure.

vascular contraction; 5-hydroxytryptamine