Pivotal role of α2 Na+ pumps and their high affinity ouabain binding site in cardiovascular health and disease.
J Physiol
; 594(21): 6079-6103, 2016 11 01.
Article
em En
| MEDLINE
| ID: mdl-27350568
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ouabaína
/
Sistema Cardiovascular
/
ATPase Trocadora de Sódio-Potássio
/
Hipertensão
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Physiol
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos