期刊
STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS
卷 20, 期 2, 页码 189-196出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10253890.2017.1296949
关键词
Angiotensin-(1-7); anxiety; emotional stressor; heart rate; renal sympathetic activity; transgenic
资金
- CNPq [PQ30600/2013-0]
- Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG)
- PRONEX
- INCT-Nanobiofar (CNPq/Fapemig)
- CAPES
- German agency DFG
- Labfar (Alamantec)
Angiotensin II (Ang II) acts as a pro-stress hormone, while other evidence indicates that angiotensin-(1-7) [Ang-(1-7)] attenuates physiological responses to emotional stress. To further test this hypothesis, in groups of 5-6 rats we evaluated autonomic, cardiovascular and behavioral parameters in male Sprague-Dawley (SD) and transgenic TGR(A1-7)3292 (TG) rats chronically overexpressing Ang-(1-7). Compared to SD rats, TG rats showed reduced baseline heart rate (HR; SD 38016 versus TG 329 +/- 9beats per minute (bpm), mean +/- standard error of mean, p<.05) and renal sympathetic discharge (SD 138 +/- 4 versus TG 117 +/- 5 spikes/second, p<.05). TG rats had an attenuated tachycardic response to acute air-puff stress (HR: SD 51 +/- 20 versus TG 1 +/- 3bpm; p<.05), which was reversed by intracerebroventricular injection of the Mas receptor antagonist, A-779 (HR: SD 51 +/- 20 versus TG 63 +/- 15bpm). TG rats showed less anxious behavior on the elevated plus maze, as revealed by more entries into open arms (SD 2 +/- 2 versus TG 47 +/- 5% relative to total entries; p<.05), and more time spent in the open arms (SD 5 +/- 4 versus TG 53 +/- 9% relative to total time, p<.05). By contrast with SD rats, diazepam (1.5mg/kg, intraperitoneally) did not further reduce anxious behavior in TG rats, indicating a ceiling anxiolytic effect of Ang-(1-7) overexpression. Ang-(1-7) concentrations in hypothalamus and plasma, measured by mass spectrometry were two- and three-fold greater, respectively, in TG rats than in SD rats. Hence, increased endogenous Ang-(1-7) levels in TG rats diminishes renal sympathetic outflow and attenuates cardiac reactivity to emotional stress, which may be via central Mas receptors, and reduces anxious behavior.Lay summaryWe used a genetically modified rat model that produces above normal amounts of a peptide hormone called angiotensin-(1-7) to test whether this peptide can reduce some of the effects of stress. We found that angiotensin-(1-7), acting in the brain, can reduce anxiety and reduce the increase in heart rate associated with emotional stress. These findings may provide a lead for design of new drugs to reduce stress.
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