Abstract
The prelimbic cortex (PL) is an important structure in the neural pathway integrating stress responses. Brain angiotensin is involved in cardiovascular control and modulation of stress responses. Blockade of angiotensin receptors has been reported to reduce stress responses. Acute restraint stress (ARS) is a stress model, which evokes sustained blood pressure increase, tachycardia, and reduction in tail temperature. We therefore hypothesized that PL locally generated angiotensin and angiotensin receptors modulate stress autonomic responses. To test this hypothesis, we microinjected an angiotensin-converting enzyme (ACE) inhibitor or angiotensin antagonists into the PL, prior to ARS. Male Wistar rats were used; guide cannulas were bilaterally implanted in the PL for microinjection of vehicle or drugs. A polyethylene catheter was introduced into the femoral artery to record cardiovascular parameters. Tail temperature was measured using a thermal camera. ARS was started 10 min after PL treatment with drugs. Pretreatment with ACE inhibitor lisinopril (0.5 nmol/100 nL) reduced the pressor response, but did not affect ARS-evoked tachycardia. At a dose of 1 nmol/100 nL, it reduced both ARS pressor and tachycardic responses. Pretreatment with candesartan, AT1 receptor antagonist reduced ARS-evoked pressor response, but not tachycardia. Pretreatment with PD123177, AT2 receptor antagonist, reduced tachycardia, but did not affect ARS pressor response. No treatment affected ARS fall in tail temperature. Results suggest involvement of PL angiotensin in the mediation of ARS cardiovascular responses, with participation of both AT1 and AT2 receptors. In conclusion, results indicate that PL AT1-receptors modulate the ARS-evoked pressor response, while AT2-receptors modulate the tachycardic component of the autonomic response.
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Abbreviations
- mPFC:
-
Medial prefrontal cortex
- PL:
-
Prelimbic cortex
- RAS:
-
Renin–angiotensin system
- ARS:
-
Acute restraint stress
- ACE:
-
Angiotensin-converting enzyme
- MAP:
-
Mean arterial pressure
- PAP:
-
Pulsatile arterial pressure
- HR:
-
Heart rate
- TT:
-
Tail temperature
- PVN:
-
Paraventricular nucleus of hypothalamus
- Ang-I:
-
Angiotensin I
- Ang-II:
-
Angiotensin II
- RVLM:
-
Rostral ventrolateral medulla
- CVLM:
-
Caudal ventrolateral medulla
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The authors would like to thank Ivanilda A.C. Fortunato for technical help.
Funding
This work was supported by grants from CNPq (474477/2013-4) and FAEPA. Brasil is a graduate student and recipient of CAPES fellowship. Fassini is a graduate student and recipient of Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) fellowship (2013/00249-9).
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T.F.B.S, A.F and F.M.C conception and design of research; T.F.B.S, A.F performed experiments; T.F.B.S, A.F analyzed the data; T.F.B.S, A.F and F.M.C interpreted results of experiments; T.F.B.S prepared figures; T.F.B.S drafted manuscript; T.F.B.S, A.F edited and revised manuscript; F.M.C approved final version of the manuscript.
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Brasil, T.F.S., Fassini, A. & Corrêa, F.M. AT1 and AT2 Receptors in the Prelimbic Cortex Modulate the Cardiovascular Response Evoked by Acute Exposure to Restraint Stress in Rats. Cell Mol Neurobiol 38, 305–316 (2018). https://doi.org/10.1007/s10571-017-0518-9
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DOI: https://doi.org/10.1007/s10571-017-0518-9