Paillé Vincent, Park Joohee, Toutain Bertrand, Bourreau Jennifer, Fontanaud Pierre, De Nardi Frédéric, Gabillard-Lefort Claudie, Bréard Dimitri, Guilet David, Henrion Daniel, Legros Christian, Guérineau Nathalie C
Univ Angers, INSERM, CNRS, MITOVASC, Équipe CARME, SFR ICAT, F-49000 Angers, France.
Nantes Université, INRAE, UMR 1280, PhAN, Nantes, France.
Cell Mol Life Sci. 2024 Dec 27;82(1):31. doi: 10.1007/s00018-024-05524-5.
Chronic elevated blood pressure impinges on the functioning of multiple organs and therefore harms body homeostasis. Elucidating the protective mechanisms whereby the organism copes with sustained or repetitive blood pressure rises is therefore a topical challenge. Here we address this issue in the adrenal medulla, the master neuroendocrine tissue involved in the secretion of catecholamines, influential hormones in blood pressure regulation. Combining electrophysiological techniques with catecholamine secretion assays on acute adrenal slices from spontaneously hypertensive rats, we show that chromaffin cell stimulus-secretion coupling is remodeled, resulting in a less efficient secretory function primarily upon sustained cholinergic challenges. The remodeling is supported by revamped both cellular and tissular mechanisms. This first includes a decrease in chromaffin cell excitability in response to sustained electrical stimulation. This hallmark was observed both experimentally and in a computational chromaffin cell model, and occurs with concomitant changes in voltage-gated ion channel expression. The cholinergic transmission at the splanchnic nerve-chromaffin cell synapses and the gap junctional communication between chromaffin cells are also weakened. As such, by disabling its competence to release catecholamines in response sustained stimulations, the hypertensive medulla has elaborated an adaptive shielding mechanism against damaging effects of redundant elevated catecholamine secretion and associated blood pressure.
慢性高血压会影响多个器官的功能，进而损害体内平衡。因此，阐明机体应对持续性或反复性血压升高的保护机制是一个热门挑战。在此，我们在肾上腺髓质中探讨这一问题，肾上腺髓质是参与儿茶酚胺分泌的主要神经内分泌组织，儿茶酚胺是血压调节中有重要作用的激素。我们将电生理技术与对自发性高血压大鼠急性肾上腺切片进行的儿茶酚胺分泌测定相结合，结果表明嗜铬细胞的刺激 - 分泌偶联发生了重塑，主要在持续性胆碱能刺激时导致分泌功能效率降低。这种重塑得到了细胞和组织机制更新的支持。首先包括嗜铬细胞对持续性电刺激的兴奋性降低。这一特征在实验和嗜铬细胞计算模型中均被观察到，并且伴随着电压门控离子通道表达的变化。内脏神经 - 嗜铬细胞突触处的胆碱能传递以及嗜铬细胞之间的缝隙连接通讯也被削弱。因此，通过丧失其在持续性刺激下释放儿茶酚胺的能力，高血压状态下的肾上腺髓质形成了一种适应性保护机制，以抵御过多儿茶酚胺分泌及相关血压升高的有害影响。
