Replacement of (alpha)1-Na-K-ATPase of Dahl rats by Milan rats lowers blood pressure but does not affect its activity.

Abstract

Both linkage and use of congenic strains have shown that a chromosome region near the gene for the Na-K-ATPase alpha(1)-subunit (Atp1a1) contained a quantitative trait locus (QTL) for blood pressure (BP). Currently, two congenic strains, designated S.M5 and S.M6, were made by replacing a segment of the Dahl salt-sensitive SS/Jr (S) rat by the homologous region of the Milan normotensive rat (MNS). In S.M5, the gene for Atp1a1 is from the MNS strain; whereas in S.M6, Atp1a1 is from the S strain. The baseline activity of the alpha(1)-Na-K-ATPase and its stoichiometry were evaluated by an assay of ouabain-sensitive inwardly and outwardly directed (86)Rb and (22)Na fluxes in erythrocytes. The two congenic strains showed a similar BP, but both had a BP lower than that of S rats (P < 0.0001). Neither the alpha(1)-Na-K-ATPase activity nor its stoichiometry was affected by the substitution of the Atp1a1 alleles of S by those of MNS. Thus the BP-lowering effects observed in S.M5 and S.M6 could not be attributed to the alpha(1)-Na-K-ATPase activity or its stoichiometry. Atp1a1 is not supported as a candidate to be a BP QTL.