In:
American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 296, No. 6 ( 2009-06), p. H1833-H1839
Abstract:
Endogenous Na + pump inhibitors are thought to play important (patho)physiological roles and occur in two different chemical forms in the mammalian circulation: cardenolides, such as ouabain, and bufadienolides, such as marinobufagenin (MBG). Although all α Na + -K + -ATPase isoforms (α 1-4 ) are sensitive to ouabain in most species, in rats and mice the ubiquitously expressed α 1 Na + -K + -ATPase is resistant to ouabain. We have previously shown that selective modification of the putative ouabain binding site of either the α 1 or α 2 Na + -K + -ATPase subunit in mice substantially alters the cardiotonic influence of exogenously applied cardenolides. To determine whether the ouabain binding site also interacts with MBG and if this interaction plays a functional role, we evaluated cardiovascular function in α 1 -resistant/α 2 -resistant (α 1 R/R α 2 R/R ), α 1 -sensitive/α 2 -resistant (α 1 S/S α 2 R/R ), and α 1 -resistant/α 2 -sensitive mice (α 1 R/R α 2 S/S , wild type). Cardiovascular indexes were evaluated in vivo by cardiac catheterization at baseline and during graded infusions of MBG. There were no differences in baseline measurements of targeted mice, indicating normal hemodynamics and cardiac function. MBG at 0.025, 0.05, and 0.1 nmol·min −1 ·g body wt −1 significantly increased cardiac performance to a greater extent in α 1 S/S α 2 R/R compared with α 1 R/R α 2 R/R and wild-type mice. The increase in LVdP/d t max in α 1 S/S α 2 R/R mice was greater at higher concentrations of MBG compared with both α 1 R/R α 2 R/R and α 1 R/R α 2 S/S mice ( P 〈 0.05). These results suggest that MBG interacts with the ouabain binding site of the α 1 Na + -K + -ATPase subunit and can thereby influence cardiac inotropy.
Type of Medium:
Online Resource
ISSN:
0363-6135
,
1522-1539
DOI:
10.1152/ajpheart.00285.2009
Language:
English
Publisher:
American Physiological Society
Publication Date:
2009
detail.hit.zdb_id:
1477308-9
SSG:
12
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