Journal of the American Heart Association · 2026
Regulation of Aldosterone Secretion by Substance P and the Neurokinin Type 1 Receptor in Aldosterone-Producing Adenomas.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Lopez Antoine-Guy, Duparc Céline, Renouf Sylvie, D'Agostino Margot, De Sousa Kelly, Amar Laurence, Defortescu Guillaume, Manceau Gilles, Sabourin Jean-Christophe, Fernandes-Rosa Fabio Luiz, Zennaro Maria-Christina, Meatchi Tchao, Nicolas Gaël, Louiset Estelle, Lefebvre Hervé
Аннотация
BACKGROUND: Aldosterone-producing adenoma (APA) is a major cause of primary aldosteronism, the most frequent form of secondary hypertension. Although somatic mutations in ion channels within APA have been shown to activate Ca2+ signaling and drive aldosterone production, the pathophysiology of primary aldosteronism remains partially understood. SP (Substance P), encoded by the TAC1 gene, is a neuropeptide of the tachykinin family, known for its role in stimulating aldosterone production through activation of the neurokinin 1 receptor (NK1R) in the human adrenal cortex. The aim of our work was to investigate the presence of SP nerve fibers and the NK1R in a large series of APA to assess the potential role of tachykinins in the pathophysiology of primary aldosteronism.
METHODS: Using molecular, immunohistochemical, and functional techniques, 56 APA tissues were analyzed to assess the expression of SP and NK1R and their impact on aldosterone secretion.
RESULTS: SP-positive nerve fibers were detected in 90% of the APA tissues, localized both within and around the adenomas, which also showed strong NK1R expression. Functional studies revealed that SP stimulated aldosterone secretion in 6 of 10 APA cultures. The NK1R antagonist aprepitant inhibited SP-induced aldosterone secretion in 3 of the 4 SP-responsive APA cultures on which the antagonist was tested. Additionally, in perifused APA explants, SP influenced aldosterone pulsatility, resulting in enhanced mineralocorticoid secretion.
CONCLUSIONS: These findings suggest that the SP-NK1R signaling pathway may contribute to APA pathophysiology and represent a novel potential target for the pharmacological treatment of PA in a subset of patients.
METHODS: Using molecular, immunohistochemical, and functional techniques, 56 APA tissues were analyzed to assess the expression of SP and NK1R and their impact on aldosterone secretion.
RESULTS: SP-positive nerve fibers were detected in 90% of the APA tissues, localized both within and around the adenomas, which also showed strong NK1R expression. Functional studies revealed that SP stimulated aldosterone secretion in 6 of 10 APA cultures. The NK1R antagonist aprepitant inhibited SP-induced aldosterone secretion in 3 of the 4 SP-responsive APA cultures on which the antagonist was tested. Additionally, in perifused APA explants, SP influenced aldosterone pulsatility, resulting in enhanced mineralocorticoid secretion.
CONCLUSIONS: These findings suggest that the SP-NK1R signaling pathway may contribute to APA pathophysiology and represent a novel potential target for the pharmacological treatment of PA in a subset of patients.