Regulation of Ion Balance by Vascular β3-Adrenergic Receptors through Endothelial Mechanisms

Year 2025, Volume: 55 Issue: 3, 404 - 410, 14.01.2026

Gizem Kaykı Mutlu , Ebru Arıoğlu İnan , Ayhanım Elif Müderrisoğlu , İrem Karaömerlioğlu , Betül Rabia Erdoğan Vadacca , Vecdi Melih Altan

https://doi.org/10.26650/IstanbulJPharm.2025.1623707

https://izlik.org/JA82NR24FZ

Abstract

Background and Aims: Vascular Na+/K+ ATPase (NKA) activity plays a crucial role in regulating vascular tone. β₃-adrenoceptors (β₃-ARs), which are upregulated during sympathetic overactivation, have been demonstrated to stimulate NKA activity in cardiac tissue. However, their role in vascular NKA regulation remains unclear. Our study aimed to investigate whether β₃-AR activation can restore NKA function in vascular tissue under high sympathetic stimulation.

Methods: Male Sprague Dawley rats were treated with noradrenaline (NA) to mimic chronic sympathetic activation, with or without BRL 37344, a β₃-AR agonist. Vascular NKA activity was assessed in the aortic rings using KCl-induced relaxation responses in K+-free buffer. The role of the endothelium was also examined.

Results: NA treatment impaired vascular NKA activity, as evidenced by reduced KCl-induced relaxation. Activation of β₃-AR restored this relaxation in an endothelium-dependent manner. In contrast, ouabain abolished the response, confirming its dependence on NKA activity.

Conclusion: These findings indicate that β₃-AR activation can restore vascular NKA activity under sympathetic stress via an endothelium-dependent mechanism. This highlights a novel vasoprotective role for β₃-ARs and support their potential as therapeutic targets in vascular pathologies associated with impaired NKA function.

Keywords

Aorta , β₃-Adrenoceptors , Endothelium , Na⁺/K⁺ ATPase

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