title: Altered Na+-K+ pump activity and plasma lipids in salt-hypertensive Dahl rats: relationship to Atp1a1 gene.
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.
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, Center for Experimental Research of Cardiovascular Diseases, CZ-142 20 Prague, Czech Republic. zicha@biomed.cas.cz
authors.forename: J
authors.initials: J
authors.lastname: Zicha
authors.forename: C D
authors.initials: CD
authors.lastname: Negrin
authors.forename: Z
authors.initials: Z
authors.lastname: Dobesová
authors.forename: F
authors.initials: F
authors.lastname: Carr
authors.forename: M
authors.initials: M
authors.lastname: Vokurková
authors.forename: M W
authors.initials: MW
authors.lastname: McBride
authors.forename: J
authors.initials: J
authors.lastname: Kunes
authors.forename: A F
authors.initials: AF
authors.lastname: Dominiczak
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D017136:Ion Transport; D008055:Lipids / Q000097:blood*; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D011110:Polymorphism, Genetic; D051381:Rats; D020303:Rats, Inbred Dahl; D012413:Rubidium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D012965:Sodium Chloride / Q000008:administration & dosage; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D008055:Lipids; D012965:Sodium Chloride; D010042:Ouabain; D002784:Cholesterol; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium