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- Title
Identification of Novel Cross-Talk between the Neuroendocrine and Autonomic Stress Axes Controlling Blood Pressure.
- Authors
Elsaafien, Khalid; Kirchner, Matthew K.; Mohammed, Mazher; Eikenberry, Sophia A.; West, Chloe; Scott, Karen A.; de Kloet, Annette D.; Stern, Javier E.; Krause, Eric G.
- Abstract
The hypothalamic paraventricular nucleus (PVN) controls neuroendocrine axes and the autonomic nervous system to mount responses that cope with the energetic burdens of psychological or physiological stress. Neurons in the PVN that express the angiotensin Type 1a receptor (PVNAgtr1a) are implicated in neuroendocrine and autonomic stress responses; however, the mechanism by which these neurons coordinate activation of neuroendocrine axes with sympathetic outflow remains unknown. Here, we use a multidisciplinary approach to investigate intra-PVN signaling mechanisms that couple the activity of neurons synthesizing corticotropin-releasinghormone (CRH) to blood pressure. We used the Cre-Lox system in male mice with in vivo optogenetics and cardiovascular recordings to demonstrate that excitation of PVNAgtr1a promotes elevated blood pressure that is dependent on the sympathetic nervous system. Next, neuroanatomical experiments found that PVNAgtr1a synthesize CRH, and intriguingly, fibers originating from PVNAgtr1a make appositions onto neighboring neurons that send projections to the rostral ventrolateral medulla and express CRH type 1 receptor (CRHR1) mRNA. We then used an ex vivo preparation that combined optogenetics, patch-clamp electrophysiology, and Ca21 imaging to discover that excitation of PVNAgtr1a drives the local, intra-PVN release of CRH, which activates rostral ventrolateral medulla-projecting neurons via stimulation of CRHR1(s). Finally, we returned to our in vivo preparation and found that CRH receptor antagonism specifically within the PVN lowered blood pressure basally and during optogenetic activation of PVNAgtr1a. Collectively, these results demonstrate that angiotensin II acts on PVNAgtr1a to conjoin hypothalamic-pituitary-adrenal axis activity with sympathetically mediated vasoconstriction in male mice.
- Subjects
HYPOTHALAMIC-pituitary-adrenal axis; BLOOD pressure; AUTONOMIC nervous system; SYMPATHETIC nervous system; ANGIOTENSIN II; PARAVENTRICULAR nucleus
- Publication
Journal of Neuroscience, 2021, Vol 41, Issue 21, p4641
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0251-21.2021