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

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.