Tissue-Specific Regulation of the Sodium Pump in DOCA-Salt Hypertension

Alterations in sodium pump activity have been associated with volume-sensitive hypertension, but little is known regarding the molecular regulation of the catalytically active α-subunit of the sodium pump in these models. We examined changes in the mRNA abundance of the α-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 α-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 α1-mRNA abundance compared with control (α1, CTL: 101.1 ± 9.3, DOCA-HS: 197.3 ± 22.9, P< .0001). DOCA-HS also induced a marked increase in both α1- and α2-mRNA in the aorta (α1, CTL: 122.5 ± 33.3 v DOCA-HS: 487.2 ± 59.9, P = .001; α2, 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 α2-, but not α1-, mRNA abundance in heart (α2, 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 α2 in the heart. Only the renal response would favor sodium reabsorption, which could contribute to the hypertensive process.