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Angiotensin type 1a receptors within the paraventricular nucleus of hypothalamus regulate cardiovascular and behavioral responsiveness to psychological stress
Author(s) -
Wang Lei,
Kloet Annette D.,
Smith Justin A.,
Hiller Helmut,
Sumners Colin,
Raizada Mohan K.,
Krause Eric G.
Publication year - 2016
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.30.1_supplement.1238.4
Subject(s) - endocrinology , medicine , hypothalamus , optogenetics , angiotensin ii , elevated plus maze , receptor , blood pressure , biology , neuroscience , anxiety , psychiatry
Neurons expressing angiotensin type 1a receptors (AT 1a ) within the paraventricular nucleus of hypothalamus (PVN) are heavily implicated in regulation of sympathetic nervous system activity (SNA). Less clear, is the role that this neuronal phenotype plays in mediating SNA, blood pressure and behavior during psychological stress. Here, we use the Cre/Lox system and in vivo optogenetics to elucidate the role of AT 1a ‐expressing neurons in cardiovascular and behavioral responses to psychological stress. Male mice expressing Cre recombinase driven by the AT 1a gene were delivered a Cre‐inducible adenoassociated virus expressing channelrhodopsin‐2 (ChR2) and enhanced yellow fluorescent protein (eYFP) into the PVN (See Figure 1). Optical excitation of AT 1a ‐expressing neurons within the PVN significantly increased systolic blood pressure in anesthetized mice. Subsequent studies utilized the Cre/Lox system to selectively delete AT 1a from PVN neurons (PVN AT 1a KO mice). Compared to littermate controls, PVN AT 1a KO mice had reduced adrenal weights and attenuated cardiovascular responses to restraint stress. Specifically, the increase in the systolic blood pressure and heart rate variability (assessed by the low frequency to high frequency ratio) was blunted at the initiation of restraint. To test whether this effect was predictive of altered anxiety‐like behavior, we assessed PVN AT 1a KO mice in the elevated plus maze (EPM) and determined that knockout mice spent more time in the open arms of the EPM but travelled similar distance relative to littermate controls. Collectively, these results suggest that AT 1a in the PVN play an important role in regulating sympatho‐cardiovascular reactivity and behavior during exposure to psychological stress. Support or Funding Information HL096830 (EGK); HL122494 (EGK); HL125805 (ADdK); HL116074 (ADdK); HL033610 (MKR); HL102033 (MKR) 1Selective expression of eYFP and ChR2 in PVN neurons expressing Cre recombinase driven by the AT 1a gene.