Role of natriuretic peptide receptor type C in Dahl salt-sensitive hypertensive rats.
The natriuretic peptide system is suggested to be involved in the pathogenesis of salt-sensitive hypertension; a recent report indicated that disruption of the atrial natriuretic peptide precursor gene caused salt-sensitive hypertension. However, natriuretic peptide receptor (NPR)-A knockout mice did not show enhanced salt sensitivity of blood pressure. The aim of the present study was to investigate the role of NPR-C, the other receptor for atrial natriuretic peptide, in increased salt sensitivity of blood pressure. Dahl salt-sensitive (DS) and salt-resistant (DR) rats were placed on a 0.3% or 8% NaCl diet for 4 weeks. Blood pressure was elevated by salt loading only in DS rats. RNase protection assay demonstrated that NPR-C transcript level in the kidney was reduced by chronic salt loading in both DR and DS rats, whereas expression of NPR-A and NPR-B was not altered. The reduction of NPR-C mRNA in response to salt loading was enhanced in DS compared with DR rats. In situ hybridization indicated that the salt-induced NPR-C change was attributed mainly to suppressed expression of NPR-C in the podocytes. NPR-C gene expression was regulated by salt loading in a tissue-specific manner; the marked decrease in NPR-C mRNA by salt loading was seen only in the kidney. These data suggest that the exaggerated salt-induced reduction of NPR-C in the kidney of DS rats may play an important role in the pathogenesis of salt hypertension in this animal, possibly related to impaired renal sodium excretion.
Nagase
M
M
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Bunkyo-ku, Japan.
Ando
K
K
Katafuchi
T
T
Kato
A
A
Hirose
S
S
Fujita
T
T
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D015152:Blotting, Northern; D001835:Body Weight; D015870:Gene Expression; D006973:Hypertension / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism*; D007536:Isomerism; D007668:Kidney / Q000503:physiopathology; D008297:Male; D045283:Natriuretic Agents / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D012965:Sodium Chloride / Q000494:pharmacology*; D014018:Tissue Distribution
D045283:Natriuretic Agents; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D012965:Sodium Chloride; D009320:Atrial Natriuretic Factor