Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=27350568
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Pivotal role of ?2 Na(+) pumps and their high affinity ouabain binding site in
cardiovascular health and disease
#MMPMID27350568
Blaustein MP
; Chen L
; Hamlyn JM
; Leenen FH
; Lingrel JB
; Wier WG
; Zhang J
J Physiol
2016[Nov]; 594
(21
): 6079-6103
PMID27350568
show ga
Reduced smooth muscle (SM)-specific ?2 Na(+) pump expression elevates basal blood
pressure (BP) and increases BP sensitivity to angiotensin II (Ang II) and dietary
NaCl, whilst SM-?2 overexpression lowers basal BP and decreases Ang II/salt
sensitivity. Prolonged ouabain infusion induces hypertension in rodents, and
ouabain-resistant mutation of the ?2 ouabain binding site (?2(R/R) mice) confers
resistance to several forms of hypertension. Pressure overload-induced heart
hypertrophy and failure are attenuated in cardio-specific ?2 knockout,
cardio-specific ?2 overexpression and ?2(R/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 ?2 Na(+) pump activity and
Ca(2+) transporter expression and, via Na(+) /Ca(2+) exchange, Ca(2+)
homeostasis. This regulates sensitivity to sympathetic activity, Ca(2+)
signalling and arterial and cardiac contraction.
free
free
free
