Mirabegron relaxes arteries from human visceral adipose tissue through antagonism of α 1 -adrenergic receptors.

Autor: De Stefano A; Department of Systems Medicine, Tor Vergata University, Roma, Italy., Schinzari F; Department of Aging, Policlinico A. Gemelli IRCCS, Roma, Italy., Di Daniele N; Department of Systems Medicine, Tor Vergata University, Roma, Italy., Sica G; Department of Experimental Medicine and Surgery, Tor Vergata University, Roma, Italy., Gentileschi P; Department of Experimental Medicine and Surgery, Tor Vergata University, Roma, Italy., Vizioli G; Department of Translational Medicine and Surgery, Catholic University, Rome, Italy., Cardillo C; Department of Aging, Policlinico A. Gemelli IRCCS, Roma, Italy; Department of Translational Medicine and Surgery, Catholic University, Rome, Italy. Electronic address: carmine.cardillo@unicatt.it., Tesauro M; Department of Systems Medicine, Tor Vergata University, Roma, Italy.
Jazyk: angličtina
Zdroj: Vascular pharmacology [Vascul Pharmacol] 2022 Oct; Vol. 146, pp. 107094. Date of Electronic Publication: 2022 Aug 05.
DOI: 10.1016/j.vph.2022.107094
Abstrakt: Aim: As inadequate perfusion has emerged as a key determinant of adipose tissue dysfunction in obesity, interest has grown regarding possible pharmacological interventions to prevent this process. Mirabegron has proved to improve insulin sensitivity and glucose homeostasis in obese humans via stimulation of β 3 -adrenoceptors which also seem to mediate endothelium-dependent vasodilation in disparate human vascular beds. We characterized, therefore, the vasomotor function of mirabegron in human adipose tissue arteries and the underlying mechanisms.
Methods: Small arteries (116-734 μm) isolated from visceral adipose tissue were studied ex vivo in a wire myograph. After vessels had been contracted, changes in vascular tone in response to mirabegron were determined under different conditions.
Results: Mirabegron did not elicit vasorelaxation in vessels contracted with U46619 or high-K + (both P > 0.05). Notably, mirabegron markedly blunted the contractile effect of the α 1 -adrenergic receptor agonist phenylephrine (P < 0.001) either in presence or absence of the vascular endothelium. The anti-contractile action of mirabegron on phenylephrine-induced vasoconstriction was not influenced by the presence of the selective β 3 -adrenoceptor blocker L-748,337 (P < 0.05); lack of involvement of β 3 -adrenoceptors was further supported by absent vascular staining for them at immunohistochemistry.
Conclusions: Mirabegron induces endothelium-independent vasorelaxation in arteries from visceral adipose tissue, likely through antagonism of α 1 -adrenoceptors.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: