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- Title
Pivotal role of α2 Na<sup>+</sup> pumps and their high affinity ouabain binding site in cardiovascular health and disease.
- Authors
Blaustein, Mordecai P.; Chen, Ling; Hamlyn, John M.; Leenen, Frans H. H.; Lingrel, Jerry B.; Wier, W. Gil; Zhang, Jin
- Abstract
Reduced smooth muscle (SM)-specific α2 Na+ pump expression elevates basal blood pressure (BP) and increases BP sensitivity to angiotensin II (Ang II) and dietary NaCl, whilst SM-α2 overexpression lowers basal BP and decreases Ang II/salt sensitivity. Prolonged ouabain infusion induces hypertension in rodents, and ouabain-resistant mutation of the α2 ouabain binding site (α2R/R mice) confers resistance to several forms of hypertension. Pressure overload-induced heart hypertrophy and failure are attenuated in cardio-specific α2 knockout, cardio-specific α2 overexpression and α2R/R mice. We propose a unifying hypothesis that reconciles these apparently disparate findings: brain mechanisms, activated by Ang II and high NaCl, regulate sympathetic drive and a novel neurohumoral pathway mediated by both brain and circulating endogenous ouabain (EO). Circulating EO modulates ouabain-sensitive α2 Na+ pump activity and Ca2+ transporter expression and, via Na+/Ca2+ exchange, Ca2+ homeostasis. This regulates sensitivity to sympathetic activity, Ca2+ signalling and arterial and cardiac contraction.
- Subjects
CARDIOVASCULAR diseases; OUABAIN; SMOOTH muscle; SODIUM/POTASSIUM ATPase; BLOOD pressure; ANGIOTENSIN II
- Publication
Journal of Physiology, 2016, Vol 594, Issue 21, p6079
- ISSN
0022-3751
- Publication type
Article
- DOI
10.1113/JP272419