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@prefix species: <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=> .
@prefix pubmed: <http://www.ncbi.nlm.nih.gov/pubmed/> .
@prefix orcid: <http://orcid.org/> .
sub:Head {
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    rdf:subject schem:Sodium ;
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sub:provenance {
  beldoc: dce:description "Approximately 61,000 statements." ;
    dce:rights "Copyright (c) 2011-2012, Selventa. All rights reserved." ;
    dce:title "BEL Framework Large Corpus Document" ;
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  sub:_6 prov:value "BACKGROUND: Previous studies have indicated that catechol-O-methyltransferase (COMT) can modulate renal dopaminergic tone. OBJECTIVE: To test the hypothesis that COMT blockade protects from salt-induced hypertension. METHODS: COMT gene-disrupted (-/-) mice and wild-type controls received a high-sodium diet (NaCl 6%) for 3 weeks. Blood pressure and heart rate were recorded by radiotelemetry. Tissue and urine samples were assessed by light microscopy and high-performance liquid chromatography. The effects of nitecapone treatment were also examined. Systolic blood pressure and heart rate during normal sodium diet were similar in COMT (-/-) and wild-type mice. The high-sodium diet increased night-time systolic and diastolic blood pressures in wild-type mice, whereas blood pressure in COMT (-/-) mice remained unaltered. In wild-type mice, the sodium-induced increase in blood pressure was completely normalized by treatment with the COMT inhibitor, nitecapone. At baseline, 24-h urinary excretion of levodopa (L-DOPA), dopamine and noradrenaline was increased by 145, 85 and 74%, respectively, in COMT (-/-) mice compared with wild-type controls. In COMT (-/-) and wild-type mice, a high-sodium diet increased urinary L-DOPA excretion by 405 and 660% (reflected as 102 and 212% increases in dopamine excretion), respectively. The absolute amounts of urinary L-DOPA and dopamine remained 60 and 20% greater in COMT (-/-) mice. The high-sodium diet did not influence renal cortical COMT activity. CONCLUSION: Our findings suggest that COMT deficiency in mice increases the availability of L-DOPA, leading to enhanced dopaminergic tone, which may be associated with resistance to salt-induced hypertension. The findings of the present study also underline the importance of COMT in the regulation of blood pressure, sodium excretion and renal dopaminergic tone." ;
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