Altered Na+-K+ pump activity and plasma lipids in salt-hypertensive Dahl rats: relationship to Atp1a1 gene.
Physiol Genomics
; 6(2): 99-104, 2001 Jul 17.
Article
em En
| MEDLINE
| ID: mdl-11459925
ABSTRACT
A genetic variant of the gene for the alpha(1)-isoform of Na(+)-K(+)-ATPase (Atp1a1) was suggested to be involved in the pathogenesis of salt hypertension in Dahl rats through altered Na(+)K(+) coupling ratio. We studied Na(+)-K(+) pump activity in erythrocytes of Dahl salt-sensitive (SS/Jr) rats in relation to plasma lipids and blood pressure (BP) and the linkage of polymorphic microsatellite marker D2Arb18 (located within intron 1 and exon 2 of Atp1a1 gene) with various phenotypes in 130 SS/Jr x SR/Jr F(2) rats. Salt-hypertensive SS/Jr rats had higher erythrocyte Na(+) content, enhanced ouabain-sensitive (OS) Na(+) and Rb(+) transport, and higher Na(+)Rb(+) coupling ratio of the Na(+)-K(+) pump. BP of F(2) hybrids correlated with erythrocyte Na(+) content, OS Na(+) extrusion, and OS Na(+)Rb(+) coupling ratio, but not with OS Rb(+) uptake. In F(2) hybrids there was a significant association indicating suggestive linkage (P < 0.005, LOD score 2.5) of an intragenic marker D2Arb18 with pulse pressure but not with mean arterial pressure or any parameter of Na(+)-K(+) pump activity (including its Na(+)Rb(+) coupling ratio). In contrast, plasma cholesterol, which was elevated in salt-hypertensive Dahl rats and which correlated with BP in F(2) hybrids, was also positively associated with OS Na(+) extrusion. The abnormal Na(+)K(+) stoichiometry of the Na(+)-K(+) pump is a consequence of elevated erythrocyte Na(+) content and suppressed OS Rb(+)K(+) exchange. In conclusion, abnormal cholesterol metabolism but not the Atp1a1 gene locus might represent an important factor for both high BP and altered Na(+)-K(+) pump function in salt-hypertensive Dahl rats.
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Base de dados:
MEDLINE
Assunto principal:
ATPase Trocadora de Sódio-Potássio
/
Hipertensão
/
Lipídeos
Limite:
Animals
Idioma:
En
Revista:
Physiol Genomics
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
República Tcheca