NADPH oxidase contributes to angiotensin II signaling in the nucleus tractus solitarius.
Angiotensin II (AngII), acting through angiotensin type 1 (AT1) receptors, exerts powerful effects on central autonomic networks regulating cardiovascular homeostasis and fluid balance; however, the mechanisms of AngII signaling in functionally defined central autonomic neurons have not been fully elucidated. In vascular cells, reactive oxygen species (ROS) generated by the enzyme NADPH oxidase play a major role in AngII signaling. Thus, we sought 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. The present studies focused on the intermediate dorsomedial nucleus of the solitary tract (dmNTS) because this region receives autonomic afferents via the vagus nerve and is an important site of AngII actions. Using double-label immunoelectron microscopy, we found that the essential NADPH oxidase subunit gp91phox is present in somatodendric and axonal profiles containing AT1 receptors. The gp91phox-labeled dendrites received inputs from large axon terminals resembling vagal afferents. In parallel experiments using patch clamp of dissociated NTS neurons anterogradely labeled via the vagus, we found that AngII potentiates the L-type Ca2+ currents, an effect mediated by AT1 receptors and abolished by the ROS scavenger Mn(III) tetrakis (4-benzoic acid) porphyrin chloride. The NADPH oxidase assembly inhibitor apocynin and the peptide inhibitor gp91phox docking sequence, 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+ influx in NTS neurons receiving vagal afferents and support the notion that ROS are important signaling molecules in central autonomic networks.
Wang
Gang
G
Division of Neurobiology, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10021, USA. gaw2001@med.cornell.edu
Anrather
Josef
J
Huang
Jie
J
Speth
Robert C
RC
Pickel
Virginia M
VM
Iadecola
Costantino
C
D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000502:physiology; D066298:In Vitro Techniques; D016253:Microscopy, Immunoelectron; D019255:NADPH Oxidases / Q000096:biosynthesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis / Q000502:physiology; D015398:Signal Transduction; D017552:Solitary Nucleus / Q000378:metabolism*; D015854:Up-Regulation; D014630:Vagus Nerve / Q000502:physiology
D020746:Calcium Channels, L-Type; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D019255:NADPH Oxidases; D002118:Calcium