Cardiovascular and pharmacological implications of haem-deficient NO-unresponsive soluble guanylate cyclase knock-in mice.
Nat Commun
; 6: 8482, 2015 Oct 07.
Article
em En
| MEDLINE
| ID: mdl-26442659
ABSTRACT
Oxidative stress, a central mediator of cardiovascular disease, results in loss of the prosthetic haem group of soluble guanylate cyclase (sGC), preventing its activation by nitric oxide (NO). Here we introduce Apo-sGC mice expressing haem-free sGC. Apo-sGC mice are viable and develop hypertension. The haemodynamic effects of NO are abolished, but those of the sGC activator cinaciguat are enhanced in apo-sGC mice, suggesting that the effects of NO on smooth muscle relaxation, blood pressure regulation and inhibition of platelet aggregation require sGC activation by NO. Tumour necrosis factor (TNF)-induced hypotension and mortality are preserved in apo-sGC mice, indicating that pathways other than sGC signalling mediate the cardiovascular collapse in shock. Apo-sGC mice allow for differentiation between sGC-dependent and -independent NO effects and between haem-dependent and -independent sGC effects. Apo-sGC mice represent a unique experimental platform to study the in vivo consequences of sGC oxidation and the therapeutic potential of sGC activators.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Sistema Cardiovascular
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Receptores Citoplasmáticos e Nucleares
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Guanilato Ciclase
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Heme
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Músculo Liso Vascular
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Óxido Nítrico
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article