Published online before print June 5, 2006, doi: 10.1161/01.HYP.0000225754.15146.dd
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(Hypertension. 2006;48:134.)
© 2006 American Heart Association, Inc.
Original Articles |
Arterial 5-Hydroxytryptamine Transporter Function Is Impaired in Deoxycorticosterone Acetate and N
-Nitro-L-Arginine But Not Spontaneously Hypertensive Rats
From the Department of Pharmacology and Toxicology, Michigan State University, East Lansing.
Correspondence to Wei Ni, Department of Pharmacology and Toxicology, B445 Life Science Building, Michigan State University, East Lansing, MI 48824-1317. E-mail niwei{at}msu.edu
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, N
-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 µmol/L) or fluvoxamine (1 µmol/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.
Key Words: rats
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