Replacement of (alpha)1-Na-K-ATPase of Dahl rats by Milan rats lowers blood pressure but does not affect its activity.
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.
Orlov
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SN
Research Centre, Centre Hospitalier de l'Université de Montreal, Hôtel Dieu, Montreal, Quebec, H2W 1T8, Canada.
Dutil
J
J
Hamet
P
P
Deng
A Y
AY
D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics*; D004789:Enzyme Activation / Q000235:genetics; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D018390:Gene Targeting; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D021122:Protein Subunits; D019655:Quantitative Trait, Heritable; D051381:Rats; D020303:Rats, Inbred Dahl; D011919:Rats, Inbred Strains; D012414:Rubidium Radioisotopes / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D012979:Sodium Radioisotopes / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
D021122:Protein Subunits; D012414:Rubidium Radioisotopes; D017673:Sodium Chloride, Dietary; D012979:Sodium Radioisotopes; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase