Angiotensin type 1A receptors in C1 neurons of the rostral ventrolateral medulla modulate the pressor response to aversive stress.
The rise in blood pressure during an acute aversive stress has been suggested to involve activation of angiotensin type 1A receptors (AT(1A)Rs) at various sites within the brain, including the rostral ventrolateral medulla. In this study we examine the involvement of AT(1A)Rs associated with a subclass of sympathetic premotor neurons of the rostral ventrolateral medulla, the C1 neurons. The distribution of putative AT(1A)R-expressing cells was mapped throughout the brains of three transgenic mice with a bacterial artificial chromosome-expressing green fluorescent protein under the control of the AT(1A)R promoter. The overall distribution correlated with that of the AT(1A)Rs mapped by other methods and demonstrated that the majority of C1 neurons express the AT(1A)R. Cre-recombinase expression in C1 neurons of AT(1A)R-floxed mice enabled demonstration that the pressor response to microinjection of angiotensin II into the rostral ventrolateral medulla is dependent upon expression of the AT(1A)R in these neurons. Lentiviral-induced expression of wild-type AT(1A)Rs in C1 neurons of global AT(1A)R knock-out mice, implanted with radiotelemeter devices for recording blood pressure, modulated the pressor response to aversive stress. During prolonged cage-switch stress, expression of AT(1A)Rs in C1 neurons induced a greater sustained pressor response when compared to the control viral-injected group (22 ± 4 mmHg for AT(1A)R vs 10 ± 1 mmHg for GFP; p < 0.001), which was restored toward that of the wild-type group (28 ± 2 mmHg). This study demonstrates that AT(1A)R expression by C1 neurons is essential for the pressor response to angiotensin II and that this pathway plays an important role in the pressor response to aversive stress.
Department of Physiology, University of Melbourne, Melbourne, Victoria 3010, Australia.
Daian
D
Chen
Nikola
N
Jancovski
Jaspreet K
JK
Bassi
Thu-Phuc
TP
Nguyen-Huu
Yan-Ting
YT
Choong
Kesia
K
Palma-Rigo
Pamela J
PJ
Davern
Susan B
SB
Gurley
Walter G
WG
Thomas
Geoffrey A
GA
Head
Andrew M
AM
Allen
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology*; D011311:Pressoreceptors / Q000502:physiology*; D044140:Receptor, Angiotensin, Type 1 / Q000819:agonists / Q000096:biosynthesis*; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology / Q000523:psychology
D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II