Adaptive remodeling of rat adrenomedullary stimulus-secretion coupling in response to a chronic hypertensive environment

Paille, V.; Park, J.; Toutain, B.; Bourreau, J.; Fontanaud, P.; De Nardi, F.; Gabillard-Lefort, C.; Breard, D.; Guilet, D.; Henrion, D.; Legros, C.; Guerineau, N. C.

doi:10.1101/2023.11.28.568973

bioRxiv · 10.1101/2023.11.28.568973

Adaptive remodeling of rat adrenomedullary stimulus-secretion coupling in response to a chronic hypertensive environment

Paille, V.·Park, J.·Toutain, B.·Bourreau, J.·Fontanaud, P.·De Nardi, F.·Gabillard-Lefort, C.·Breard, D.·Guilet, D.·Henrion, D.·Legros, C.·Guerineau, N. C.

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Abstract

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. Using 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 electrical or cholinergic challenges. The remodeling is supported by revamped cellular and tissular mechanisms, including chromaffin cell excitability through voltage-gated ion channel expression changes, gap junctional communication and cholinergic synaptic transmission. As such, by weakening its competence to release catecholamines, the hypertensive medulla has elaborated an adaptive shielding mechanism against damaging effects of redundant elevated catecholamine secretion and associated blood pressure.

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Paille, V., Park, J., Toutain, B., Bourreau, J., Fontanaud, P., De Nardi, F., Gabillard-Lefort, C., Breard, D., Guilet, D., Henrion, D., Legros, C., Guerineau, N. C.. 2023-11-28. Adaptive remodeling of rat adrenomedullary stimulus-secretion coupling in response to a chronic hypertensive environment. https://doi.org/10.1101/2023.11.28.568973

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