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The specific aims of my recent research are to use ultrastructural and functional approaches to determine whether reactive oxygen species (ROS) are involved in Angiotensin II (AngII) signaling in well-characterized central autonomic neurons and to define their enzymatic source to determine whether NADPH oxidase is present in central autonomic neurons and, if so, whether NADPH oxidase-derived ROS are involved in the effects of AngII on these neurons. These studies focused on the dorsomedial nucleus of the solitary tract (dmNTS) because this region receives afferents from arterial baroreceptors and cardiopulmonary receptors via the vagus nerve, and is critical for maintaining cardiovascular homeostasis. Using double-label immunoelectronmicroscopy we have found that the essential NADPH oxidase subunit gp91phox is present in NTS neurons receiving vagal-like afferents that also contain AT1 receptors. In parallel experiments using electrophysiological approaches of dissociated dmNTS neurons anterogradely labeled via the vagus, I have found that AngII potentiates the L-type Ca2+ currents, an effect mediated by AT1 receptors and abolished by the ROS scavenger MnTBAP. The NADPH oxidase assembly inhibitor apocynin and the peptide inhibitor gp91ds, but not its scrambled version, also blocked the potentiation. The results provide evidence that NADPH oxidase-derived ROS are involved in the effects of AngII on Ca2+ signaling in dmNTS neurons receiving vagal afferents, and support the notion that ROS are important signaling molecules in central autonomic networks.
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Nature Neuroscienceno. 1 (2024): 63-77
Costantino Iadecola,Antoine Anfray,Samantha Schaeffer,Yorito Hattori,Monica Santisteban, Nicole Casey,Gang Wang, Michael Strickland,Ping Zhou,David Holtzman,Josef Anrather,Laibaik Park
Research square (2023)
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Neurochemistry international (2022): 105420-105420
Monica M. Santisteban,Giuseppe Faraco, David Brea Lopez,Gang Wang, Melissa Sobanko,Rose Sciortino,Gianfranco Racchumi,Ari Waisman,Josef Anrather,Costantino Iadecola
biorxiv(2022)
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