RENAL NA,K-ATPASE IN GENETIC-HYPERTENSION

Milan hypertensive rats (MHS) develop hypertension because of a primar y renal alteration Both apical and basolateral sodium transport are fa ster in membrane vesicles derived from renal tubules of MHS than in th ose of Milan normotensive control rats (MNS). These findings suggest t hat the increased renal sodium retention and concomitant development o f hypertension in MHS may be linked to an altered transepithelial sodi um transport. Since this transport is mainly under the control of the Na-K pump, we investigated whether an alteration of the enzymatic acti vity and/or protein expression of the renal Na,K-ATPase is detectable in prehypertensive MHS. We measured the Na,K-ATPase activity, Rb+ occl usion, turnover number, alpha(1)- and beta(1)-subunit protein abundanc e, and alpha(1) and beta(1) mRNA levels in microsomes from renal outer medulla of young (prehypertensive) and adult (hypertensive) MHS and i n age-matched MNS. In both young and adult MHS, the Na, K-ATPase activ ity was significantly higher because of an enhanced number of active p ump sites, as determined by Rb+ occlusion maximal binding. The higher number of pump sites was associated with a significant pretranslationa l increase of alpha(1) and beta(1) mRNA levers that preceded the devel opment of hypertension in MHS. Since a molecular alteration of the cyt oskeletal protein adducin is genetically associated with hypertension in MHS and is able to affect the actin-cytoskeleton and Na-Ii pump act ivity in transfected renal cells, we propose that the in vivo upregula tion of Na-K pump in MHS is primary and linked to a genetic alteration of adducin.