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We reported upregulation of the 5-hydroxytryptamine (HT) transporter (5-HTT) protein in peripheral arteries from deoxycorticosterone acetate (DOCA)-salt hypertensive rats. We hypothesized that upregulated 5-HTT may be generally elevated in hypertensive models and, as a consequence, a higher basal concentration of 5-HT, the 5-HT metabolite 5-hydroxyindoleacetic acid, and an increased 5-HT uptake would occur in peripheral arteries of hypertensive rats compared with normotensive rats. We examined 3 hypertension models: DOCA-salt rats, Nomega-nitro-L-arginine (LNNA) rats, and spontaneously hypertensive rats (SHRs) in our study (systolic blood pressure [mm Hg]: DOCA (D)=197+/-6, SHAM(D)=112+/-4, LNNA (L)=228+/-9, SHAM(L)=128+/-2, SHR=172+/-7, and Wistar-Kyoto [WKY]= 121+/-3). High-pressure liquid chromatography measurements showed lower basal 5-HT concentrations in aorta from DOCA-salt and LNNA rats compared with their SHAM rats but not in SHR compared with WKY. In all of the 5-HT-uptake studies, we used arteries isolated from rats treated with the monoamine oxidase-A inhibitor pargyline to minimize 5-HT metabolism. Exogenous 5-HT was taken up by aorta, and this was inhibited by the 5-HTT inhibitor fluoxetine (1 micromol/L) or fluvoxamine (1 micromol/L). Total 5-HT uptake and 5-HTT-dependent active 5-HT uptake were decreased in aorta from DOCA-salt and LNNA rats compared with SHAM rats, but this was not observed in SHRs compared with WKYs. Western analysis revealed similar expression of 5-HTT in aorta from WKYs and SHRs as opposed to an upregulated 5-HTT in aorta from DOCA-salt and LNNA-hypertensive rats. Our study suggested that an altered serotonergic system by impaired 5-HTT function might play a role in blood pressure regulation in DOCA-salt and LNNA-hypertensive rats.

hypertension

Arterial 5-Hydroxytryptamine Transporter Function Is Impaired in Deoxycorticosterone Acetate and Nω-Nitro- <scp>l</scp> -Arginine But Not Spontaneously Hypertensive Rats

Arterial 5-Hydroxytryptamine Transporter Function Is Impaired in Deoxycorticosterone Acetate and Nω-Nitro- l -Arginine But Not Spontaneously Hypertensive Rats