Renal Na,K-ATPase in genetic hypertension.
Milan hypertensive rats (MHS) develop hypertension because of a primary renal alteration. Both apical and basolateral sodium transport are faster in membrane vesicles derived from renal tubules of MHS than in those of Milan normotensive control rats (MNS). These findings suggest that the increased renal sodium retention and concomitant development of hypertension in MHS may be linked to an altered transepithelial sodium transport. Since this transport is mainly under the control of the Na-K pump, we investigated whether an alteration of the enzymatic activity and/or protein expression of the renal Na,K-ATPase is detectable in prehypertensive MHS. We measured the Na,K-ATPase activity, Rb+ occlusion, turnover number, alpha 1- and beta 1-subunit protein abundance, and alpha 1 and beta 1 mRNA levels in microsomes from renal outer medulla of young (prehypertensive) and adult (hypertensive) MHS and in age-matched MNS. In both young and adult MHS, the Na,K-ATPase activity was significantly higher because of an enhanced number of active pump sites, as determined by Rb+ occlusion maximal binding. The higher number of pump sites was associated with a significant pretranslational increase of alpha 1 and beta 1 mRNA levels that preceded the development of hypertension in MHS. Since a molecular alteration of the cytoskeletal protein adducin is genetically associated with hypertension in MHS and is able to affect the actin-cytoskeleton and Na-K pump activity in transfected renal cells, we propose that the in vivo upregulation of Na-K pump in MHS is primary and linked to a genetic alteration of adducin.
Ferrandi
M
M
Prassis-Sigma Tau Research Institute, Settimo M.se, Milan, Italy.
Tripodi
G
G
Salardi
S
S
Florio
M
M
Modica
R
R
Barassi
P
P
Parenti
P
P
Shainskaya
A
A
Karlish
S
S
Bianchi
G
G
Ferrari
P
P
D000375:Aging / Q000378:metabolism; D000818:Animals; D046508:Culture Techniques; D006973:Hypertension / Q000201:enzymology* / Q000235:genetics*; D007679:Kidney Medulla / Q000201:enzymology*; D008861:Microsomes / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D012333:RNA, Messenger; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase