Premium
Potent Blood Pressure Lowering Effect of Optogenetic Stimulation of ‘Angiotensin‐sensitive’ Neurons within the Nodose Ganglion
Author(s) -
Silva Souza Gean Domingos B,
Bruce Erin B.,
Hiller Helmut,
Smeltzer Michael D.,
Tan Yalun,
Brandi Igor Viana,
Sumners Colin,
Raizada Mohan K,
Krause Eric G.,
Kloet Annette D
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1071.1
Subject(s) - nodose ganglion , optogenetics , baroreceptor , stimulation , channelrhodopsin , angiotensin ii , neuroscience , population , medicine , vagus nerve , blood pressure , renin–angiotensin system , biology , endocrinology , chemistry , heart rate , environmental health
Neurons within the nodose ganglion (NG) convey baroreceptor status to the brain and their stimulation is known to reduce blood pressure and heart rate; however, whether a distinct population of angiotensin‐sensitive neurons within the NG mediate these effects is not clear. Here, we use neuroanatomical and optogenetic techniques to test the hypothesis that angiotensin type 1‐a receptor (AT1a)‐expressing neurons within the NG influence hemodynamic responses in male mice. Initial neuroanatomical studies revealed that AT1a‐containing neurons are localized to the NG and uncovered a dense localization of terminals arising from AT1a neurons to the intermediate nucleus of the solitary tract, consistent with their localization to the vagal afferent neurons of the NG. To examine the functional relevance of these distinct angiotensin sensitive neurons, the Cre/Lox system was then used to generate male mice expressing channelrhodopsin‐2 and yellow fluorescent protein (eYFP) specifically in AT1a‐expressing neurons. These mice (n=6) were catheterized into the left carotid artery and the left NG was identified and isolated from adjacent tissues in order to optogenetically stimulate AT1a‐containing neurons within the area. Consistent with our hypothesis, photo‐activation (473nm blue light;1, 15 or 30Hz; 1 min) of these AT1a‐expressing neurons led to significant decreases in mean arterial pressure (MAP, Δ= −16±3, −36±4 and −44±7 mmHg) and heart rate (HR, Δ= −13±7, −104±44 and −163±59 bpm) in AT1a‐ChR2‐eYFP mice but not in control mice subjected to the same stimulation parameters. Collectively, our results demonstrate that activation of AT1a‐expressing neurons in NG effectively reduces MAP and HR in mice, suggesting that AT1a in the NG might play an important role in cardiovascular equilibrium. Support or Funding Information National Heart, Lung, and Blood Institute Grant HL122494 (EGK), HL125805 (ADdK), HL‐033610 (CS and MKR)