RGD Reference Report - Suppression of catechol-O-methyltransferase activity through blunting of alpha2-adrenoceptor can explain hypertension in Dahl salt-sensitive rats. - Rat Genome Database

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Suppression of catechol-O-methyltransferase activity through blunting of alpha2-adrenoceptor can explain hypertension in Dahl salt-sensitive rats.

Authors: Hirano, Y  Tsunoda, M  Shimosawa, T  Matsui, H  Fujita, T  Funatsu, T 
Citation: Hirano Y, etal., Hypertens Res. 2007 Mar;30(3):269-78.
RGD ID: 8662344
Pubmed: PMID:17510509   (View Abstract at PubMed)
DOI: DOI:10.1291/hypres.30.269   (Journal Full-text)

Catecholamines have been reported to be involved in the development of salt-sensitive hypertension. We investigated the relation between catechol-O-methyltransferase (COMT) and salt-sensitivity. In the first experiment, Dahl salt-sensitive (DS) rats were given a normal-salt (NS), high-salt (HS), or HS+hydralazine (80 mg/l water) diet for 4 or 13 weeks, and Dahl salt-resistant (DR) rats were given a NS or HS diet. COMT activities in both the kidneys and liver and urinary norepinephrine (NE) and dopamine (DA) excretion were measured. In the second experiment, HepG2 cells were used to investigate the role of NE in regulating COMT activity. In the third experiment, we investigated the reactivity of pre- and postsynaptic alpha(2)-adrenoceptor (AR) in DS rats. HS loading significantly suppressed the activities of membrane-bound COMT (MB-COMT) and, consistent with this finding, increased the urinary NE level in DS rats, but not in DR rats. Hydralazine did not restore the MB-COMT activities, which suggested that HS loading rather than elevated blood pressure suppressed the MB-COMT activities. The in vitro experiment using HepG2 cells revealed that NE increased the MB-COMT activity via the alpha(2)-AR. However, both the pre- and postsynaptic alpha(2)-AR reactivity was decreased by HS loading in DS rats. In conclusion, HS intake suppresses the MB-COMT activities in DS rats, presumably by blunting alpha(2)-AR signaling. The suppression of MB-COMT activities, consequent decrease in degradation of NE, and increase in NE release by blunting of alpha(2)-AR function may be involved in the development of salt-sensitive hypertension in DS rats, in whom DA-dependent natriuresis may be suppressed.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypertension  ISOComt (Rattus norvegicus)8662344; 8662344 RGD 
hypertension  IDA 8662344 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Comt  (catechol-O-methyltransferase)

Genes (Mus musculus)
Comt  (catechol-O-methyltransferase)

Genes (Homo sapiens)
COMT  (catechol-O-methyltransferase)


Additional Information