title: Alterations in alpha subunit expression of cardiac Na+,K+-ATPase in spontaneously hypertensive rats: effect of antihypertensive therapy.
abstract: The alpha-2 subunit abundance of Na+,K(+)-ATPase in the rat heart has been reported to be reduced in several induced hypertensive models. To determine whether this reduction also occurs in a genetic model of hypertension, we studied expression of the alpha subunits in left ventricles of spontaneously hypertensive rats (SHR), and normotensive Wistar-Kyoto (WKY) and Sprague-Dawley rats using Western blotting and quantitative dot-blotting analysis with monoclonal antibodies. While the alpha-1 subunit was not affected in any of the strains, a significant reduction of the alpha-2 subunit expression was noted in 19-week-old SHRs, but not in age-matched WKY and Sprague-Dawley rats, supporting the hypothesis that elevated arterial pressure may differentially downregulate the alpha-2 subunit in the rat heart. To further test this hypothesis we designed experiments in which hypertensive rats were treated with the antihypertensive agents hydralazine and nifedipine. Both agents effectively normalized the blood pressure in the SHRs with no significant effect on the blood pressure in the WKY and Sprague-Dawley rats. The alpha-2 subunit in SHRs treated with hydralazine and nifedipine showed a 63.3% (n = 6, P < 0.05, analysis of variance and Fischer's test) and a 27.4% increase, respectively, over the hypertensive SHR controls, although the reversal effect of nifedipine did not quite reach significance. The alpha-1 subunit expression was not affected by any of the drug treatments. No effect of either of the drugs on the alpha-1 or alpha-2 subunit was observed in the WKY or Sprague-Dawley rat groups. These data support our hypothesis that the alpha-2 subunit may be a pressure-sensitive isoform of the cardiac Na+,K(+)-ATPase and that high blood pressure is, directly or indirectly, responsible for the reduction of the alpha-2 subunit protein expression.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Louisiana State University Medical Center, New Orleans 70112, USA.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: E
authors.initials: E
authors.lastname: Songu-Mize
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D006830:Hydralazine; D000254:Sodium-Potassium-Exchanging ATPase; D009543:Nifedipine