Altered Na+-K+ pump activity and plasma lipids in salt-hypertensive Dahl rats: relationship to Atp1a1 gene

1 Institute of Physiology, Academy of Sciences of the Czech Republic, Center for Experimental Research of Cardiovascular Diseases, CZ-142 20 Prague, Czech Republic 2 Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow G11 6NT, United Kingdom A genetic variant of the gene for the 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. F 2 hybrids; erythrocyte ion transport; erythrocyte sodium content; plasma cholesterol; rat chromosome 2; 1 -Na + -K + -ATPase gene