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Article Dans Une Revue International Journal of Molecular Sciences Année : 2023

Elevated Blood Pressure Occurs without Endothelial Dysfunction in a Rat Model of Pulmonary Emphysema

Résumé

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease involving airway closure and parenchyma destruction (emphysema). Cardiovascular diseases are the main causes of morbi-mortality in COPD and, in particular, hypertension and heart failure with preserved ejection fraction (HFpEF). However, no mechanistic link has currently been established between the onset of COPD, elevated blood pressure (BP) and systemic vascular impairment (endothelial dysfunction). Thus, we aimed to characterize BP and vascular function and remodeling in a rat model of exacerbated emphysema focusing on the role of sympathetic hyperactivity. Emphysema was induced in male Wistar rats by four weekly pulmonary instillations of elastase (4UI) and exacerbation by a single dose of lipopolysaccharides (LPS). Five weeks following the last instillation, in vivo and ex vivo cardiac and vascular functions were investigated. Exacerbated emphysema induced cardiac dysfunction (HFpEF) and a BP increase in this COPD model. We observed vasomotor changes and hypotrophic remodeling of the aorta without endothelial dysfunction. Indeed, changes in contractile and vasorelaxant properties, though endothelium-dependent, were pro-relaxant and NO-independent. A β1-receptor antagonist (bisoprolol) prevented HFpEF and vascular adaptations, while the effect on BP increase was partial. Endothelial dysfunction would not trigger hypertension and HFpEF in COPD. Vascular changes appeared as an adaptation to the increased BP. The preventing effect of bisoprolol revealed a pivotal role of sympathetic hyperactivation in BP elevation. The mechanistic link between HFpEF, cardiac sympathetic activation and BP deserves further studies in this exacerbated-emphysema model, as well as in COPD patients.
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Dates et versions

hal-04188767 , version 1 (28-08-2023)

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Elodie Desplanche, Pierre-Edouard Grillet, Quentin Wynands, Patrice Bideaux, Laurie Alburquerque, et al.. Elevated Blood Pressure Occurs without Endothelial Dysfunction in a Rat Model of Pulmonary Emphysema. International Journal of Molecular Sciences, 2023, 24 (16), pp.12609. ⟨10.3390/ijms241612609⟩. ⟨hal-04188767⟩
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