Endothelium alteration is a key process in the development of heart failure with preserved ejection fraction - 26/03/18
Résumé |
Introduction |
Endothelial has been suggested to play an important role in the development of heart failure with preserved ejection fraction (HFpEF), but there is no real link so far. Mechanism could involve alteration in vascular structure and reactivity. •NO bioavailability has been suggested to play a central role in this phenomenon and •NO production is partly mediated through β3-adrenoreceptor (β3-AR) activation. Our team developed a transgenic rat (Tgβ3) overexpressing the human β3-AR in the endothelium leading with ageing to HFpEF.
Objective |
The aim of our study was to understand the implication of the endothelium in HFpEF development.
Methods |
Aorta from 45 weeks old rat have been used to evaluate arterial reactivity (aorta and mesenteric rings). Endothelium-dependent relaxation to isoproterenol (0.1nM to 100μM) was measured in the presence or absence of •NO synthase (NOS) inhibitors: L-VNIO (NOS-1), 1400W (NOS-2) and L-NIO (NOS-3) at 10μM. •NO production in aorta has been evaluated by electron paramagnetic resonance (EPR).
Results |
Concentration-dependent vasodilation to isoproterenol was significantly reduced in Tgβ3 aorta and mesenteric arteries (−10%, P<0.05 vs. WT) indicating an alteration of endothelial function. With NOS-2 inhibitor, concentration-dependent vasodilation to isoproterenol was unchanged, but vasodilation in presence of NOS-1 and NOS-3 inhibitors was significantly reduced in Tgβ3. Interestingly, vascular production of •NO was increase in Tgβ3 rats (+91%, P<0.05 vs. WT) while, the main NOS responsible to •NO production, NOS-3, was significantly decreased (−19%, P<0.05 vs. WT).
Conclusion |
Our animal model demonstrates for the first time that alteration of the endothelial function could lead to HFpEF development. This observation could lead a better understanding of HFpEF pathophysiology, yet evolution of vascular function and •NO production need to be evaluated at different time of HFpEF development.
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Vol 10 - N° 2
P. 199 - avril 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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