Blood-borne angiotensin II acts in the brain to influence behavioral and endocrine responses to psychogenic stress.
This study elucidates the neural circuits by which circulating angiotensin II (ANGII) acts in the brain to influence humoral and behavioral responses to psychological stressors. To test the hypothesis that systemic ANGII mediates stress responding via the subfornical organ (SFO), we first found that the timing of increased systemic ANGII in response to 60 min restraint coincides with increased c-fos mRNA expression in the SFO. Next, we administered an anterograde neuronal tract tracer into the SFO and found that fibers originating there make appositions onto neurons in the paraventricular nucleus of the hypothalamus that are also c-fos positive following restraint stress. To determine whether circulating ANGII stimulates the release of stress hormones via activation of angiotensin type 1 receptors (AT1R) within the SFO, we delivered lentivirus to knockdown AT1R expression locally in the SFO. Inhibition of AT1R specifically within the SFO blunted the release of adrenocorticotrophin-releasing hormone and corticosterone in response to restraint stress and caused rats to spend more time in the open arms of an elevated-plus maze than controls, indicating that inhibition of AT1R within the SFO is anxiolytic. Collectively, these results suggest that circulating ANGII acts on AT1R in the SFO to influence responding to psychological stressors.
Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, Florida 32610, USA. ekrause@cop.ufl.edu
Eric G
EG
Krause
Annette D
AD
de Kloet
Karen A
KA
Scott
Jonathan N
JN
Flak
Kenneth
K
Jones
Michael D
MD
Smeltzer
Yvonne M
YM
Ulrich-Lai
Stephen C
SC
Woods
Steven P
SP
Wilson
Lawrence P
LP
Reagan
James P
JP
Herman
Randall R
RR
Sakai
D000704:Analysis of Variance; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D004703:Endocrine System / Q000187:drug effects*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006728:Hormones / Q000097:blood; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D013356:Subfornical Organ / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014161:Transduction, Genetic
D006728:Hormones; D010835:Phytohemagglutinins; D044140:Receptor, Angiotensin, Type 1; C100156:leukoagglutinins, plants; D000804:Angiotensin II; D049452:Green Fluorescent Proteins