TISSUE-SPECIFIC REGULATION OF THE SODIUM-PUMP IN DOCA-SALT HYPERTENSION

Alterations in sodium pump activity have been associated with volume-s ensitive hypertension, but little is known regarding the molecular reg ulation of the catalytically active alpha-subunit of the sodium pump i n these models. We examined changes in the mRNA abundance of the alpha -isoforms in tissues that might participate in sodium and volume regul ation in the deoxycorticosterone acetate (DOCA)-high salt rat model. T hese tissues included kidney, heart, aorta, pituitary, and hypothalamu s. This study assessed alterations arising from changes in dietary sal t intake alone, from DOCA administration alone, and those requiring bo th DOCA and high salt with their attendant volume expansion and hypert ension. 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 a-isoforms in any o f the tissues studied. The combination of DOCA and high salt (HS), on the other hand, brought about a twofold increase in renal alpha(1)-mRN A abundance compared with control alpha(1), CTL: 101.1 +/- 9.3, DOCA-H S: 197.3 +/- 22.9, P < .0001). DOCA-HS also induced a marked increase in both alpha(1)- and alpha(2)-mRNA in the aorta (alpha(1), CTL: 122.5 +/- 33.3 v DOCA-HS: 487.2 +/- 59.9, P = .001; alpha(2), CTL: 126.6 +/ - 40.0 v DOCA-HS: 559.8 +/- 271.7, P = .01). In contrast DOCA-IIS anim als showed a significant reduction in the alpha(2)-, but not alpha(1)- mRNA abundance in heart (alpha(2), CTL: 118.0 +/- 11.7 v DOCA-HS: 61. 1 +/- 9.1, P = .006). No change was observed in pituitary or hypothala mus with DOCA-HS. Of factors known to modulate the mRNA abundance of t he sodium pump, only the putative endogenous sodium pump inhibitor mig ht account for the changes in the aorta and kidney. Reductions in aldo sterone or hypertension might reduce alpha(2) in the heart. Only the r enal response would favor sodium reabsorption, which could contribute to the hypertensive process. (C) 1997 American Journal of Hypertension , Ltd.