title: Tissue-specific regulation of the sodium pump in DOCA-salt hypertension.
abstract: Alterations in sodium pump activity have been associated with volume-sensitive hypertension, but little is known regarding the molecular regulation of the catalytically active alpha-subunit of the sodium pump in these models. We examined changes in the mRNA abundance of the alpha-isoforms in tissues that might participate in sodium and volume regulation in the deoxycorticosterone acetate (DOCA)-high salt rat model. These tissues included kidney, heart, aorta, pituitary, and hypothalamus. This study assessed alterations arising from changes in dietary salt intake alone, from DOCA administration alone, and those requiring both DOCA and high salt with their attendant volume expansion and hypertension. Increased sodium intake produced no significant change in any isoform in the five tissues studied. DOCA administered with a low salt diet produced no significant change in any of the alpha-isoforms in any of the tissues studied. The combination of DOCA and high salt (HS), on the other hand, brought about a twofold increase in renal alpha1-mRNA abundance compared with control (alpha1, CTL: 101.1 +/- 9.3, DOCA-HS: 197.3 +/- 22.9, P < .0001). DOCA-HS also induced a marked increase in both alpha1- and alpha2-mRNA in the aorta (alpha1, CTL: 122.5 +/- 33.3 v DOCA-HS: 487.2 +/- 59.9, P = .001; alpha2, CTL: 126.6 +/- 40.0 v DOCA-HS: 559.8 +/- 271.7, P = .01). In contrast DOCA-HS animals showed a significant reduction in the alpha2-, but not alpha1-, mRNA abundance in heart (alpha2, CTL: 118.0 +/- 11.7 v DOCA-HS: 61.1 +/- 9.1, P = .006). No change was observed in pituitary or hypothalamus with DOCA-HS. Of factors known to modulate the mRNA abundance of the sodium pump, only the putative endogenous sodium pump inhibitor might account for the changes in the aorta and kidney. Reductions in aldosterone or hypertension might reduce alpha2 in the heart. Only the renal response would favor sodium reabsorption, which could contribute to the hypertensive process.
authors.affiliation: Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Soszynski
authors.forename: Q F
authors.initials: QF
authors.lastname: Tao
authors.forename: N K
authors.initials: NK
authors.lastname: Hollenberg
authors.forename: S W
authors.initials: SW
authors.lastname: Graves
mesh_terms: D000818:Animals; D003900:Desoxycorticosterone / Q000494:pharmacology*; D006973:Hypertension / Q000378:metabolism*; D007527:Isoenzymes / Q000032:analysis*; D008297:Male; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis* / Q000235:genetics
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; D003900:Desoxycorticosterone; D000254:Sodium-Potassium-Exchanging ATPase