A potential role for the endothelin ETA receptor in salt-sensitive hypertension of the proANP gene-disrupted mouse.
Mol Cell Biochem
; 275(1-2): 57-66, 2005 Jul.
Article
en En
| MEDLINE
| ID: mdl-16335784
We have previously shown that the partial disruption of the gene for atrial natriuretic peptide (ANP) results in a salt-sensitive phenotype. The present study examined the possibility that alterations in either the ANP natriuretic pathway or endothelin (ET) system in the kidney of the salt-challenged ANP +/- mouse was responsible for its salt-sensitive phenotype. Plasma ANP levels and renal cGMP activity were increased in response to a salt load in both ANP +/+ and +/- mice. However, the mRNA expression of proANP was found to be increased only in the ANP +/- kidney along with its guanylyl cyclase-linked receptor, NPRA; the upregulation of NPRA mRNA was limited to the renal medulla. This suggests that the renal ANP pathway remains capable of responding to a salt load in the ANP +/- animal, but may be compensating for other dysfunctional pathways. We also report a significant increase in renal ET-1 mRNA and ETA receptor protein expression in medulla and cortex of the salt-treated, ANP +/- mouse, but not its wild-type counterpart. In fact, ETA expression decreased in the renal cortex of the ANP +/+ salt-treated animal. The ETB receptor expression was not affected by diet in either genotype. We hypothesize that the salt-sensitive hypertension in the ANP +/- mouse is exacerbated, and possibly driven by the vasoconstrictive effects resulting from an upregulated ET-1/ETA pathway.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sodio en la Dieta
/
Factor Natriurético Atrial
/
Receptor de Endotelina A
/
Hipertensión
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Mol Cell Biochem
Año:
2005
Tipo del documento:
Article
País de afiliación:
Canadá
Pais de publicación:
Países Bajos