TY - JOUR
T1 - Sodium pump α2 subunits control myogenic tone and blood pressure in mice
AU - Zhang, Jin
AU - Lee, Moo Yeol
AU - Cavalli, Maurizio
AU - Chen, Ling
AU - Berra-Romani, Roberto
AU - Balke, C. William
AU - Bianchi, Giuseppe
AU - Ferrari, Patrizia
AU - Hamlyn, John M.
AU - Iwamoto, Takahiro
AU - Lingrel, Jerry B.
AU - Matteson, Donald R.
AU - Wier, W. Gil
AU - Blaustein, Mordecai P.
PY - 2005/11/15
Y1 - 2005/11/15
N2 - A key question in hypertension is: How is long-term blood pressure controlled? A clue is that chronic salt retention elevates an endogenous ouabain-like compound (EOLC) and induces salt-dependent hypertension mediated by Na+/Ca2+ exchange (NCX). The precise mechanism, however, is unresolved. Here we study blood pressure and isolated small arteries of mice with reduced expression of Na+ pump α1 (α1+/-) or α2 (α2+/-) catalytic subunits. Both low-dose ouabain (1-100 nM; inhibits only α2) and high-dose ouabain (≥1 μM; inhibits α1) elevate myocyte Ca2+ and constrict arteries from α1+/-, as well as α2+/- and wild-type mice. Nevertheless, only mice with reduced α2 Na+ pump activity (α2+/-), and not α1 (α1+/-), have elevated blood pressure. Also, isolated, pressurized arteries from α2+/-, but not α1+/-, have increased myogenic tone. Ouabain antagonists (PST 2238 and canrenone) and NCX blockers (SEA0400 and KB-R7943) normalize myogenic tone in ouabain-treated arteries. Only the NCX blockers normalize the elevated myogenic tone in α2+/- arteries because this tone is ouabain independent. All four agents are known to lower blood pressure in salt-dependent and ouabain-induced hypertension. Thus, chronically reduced α2 activity (α2+/- or chronic ouabain) apparently regulates myogenic tone and long-term blood pressure whereas reduced α1 activity (α1+/-) plays no persistent role: the in vivo changes in blood pressure reflect the in vitro changes in myogenic tone. Accordingly, in salt-dependent hypertension, EOLC probably increases vascular resistance and blood pressure by reducing α2 Na+ pump activity and promoting Ca2+ entry via NCX in myocytes.
AB - A key question in hypertension is: How is long-term blood pressure controlled? A clue is that chronic salt retention elevates an endogenous ouabain-like compound (EOLC) and induces salt-dependent hypertension mediated by Na+/Ca2+ exchange (NCX). The precise mechanism, however, is unresolved. Here we study blood pressure and isolated small arteries of mice with reduced expression of Na+ pump α1 (α1+/-) or α2 (α2+/-) catalytic subunits. Both low-dose ouabain (1-100 nM; inhibits only α2) and high-dose ouabain (≥1 μM; inhibits α1) elevate myocyte Ca2+ and constrict arteries from α1+/-, as well as α2+/- and wild-type mice. Nevertheless, only mice with reduced α2 Na+ pump activity (α2+/-), and not α1 (α1+/-), have elevated blood pressure. Also, isolated, pressurized arteries from α2+/-, but not α1+/-, have increased myogenic tone. Ouabain antagonists (PST 2238 and canrenone) and NCX blockers (SEA0400 and KB-R7943) normalize myogenic tone in ouabain-treated arteries. Only the NCX blockers normalize the elevated myogenic tone in α2+/- arteries because this tone is ouabain independent. All four agents are known to lower blood pressure in salt-dependent and ouabain-induced hypertension. Thus, chronically reduced α2 activity (α2+/- or chronic ouabain) apparently regulates myogenic tone and long-term blood pressure whereas reduced α1 activity (α1+/-) plays no persistent role: the in vivo changes in blood pressure reflect the in vitro changes in myogenic tone. Accordingly, in salt-dependent hypertension, EOLC probably increases vascular resistance and blood pressure by reducing α2 Na+ pump activity and promoting Ca2+ entry via NCX in myocytes.
UR - http://www.scopus.com/inward/record.url?scp=28244497641&partnerID=8YFLogxK
U2 - 10.1113/jphysiol.2005.091801
DO - 10.1113/jphysiol.2005.091801
M3 - Article
C2 - 16166162
AN - SCOPUS:28244497641
SN - 0022-3751
VL - 569
SP - 243
EP - 256
JO - Journal of Physiology
JF - Journal of Physiology
IS - 1
ER -