TY - JOUR
T1 - Role of angiotensin-(1-7) and Mas-R-nNOS pathways in amplified neuronal activity of dorsolateral periaqueductal gray after chronic heart failure
AU - Xing, Jihong
AU - Lu, Jian
AU - Li, Jianhua
N1 - Funding Information:
This study was supported by NIH R01 HL090720 and AHA Established Investigator Award 0840130N .
PY - 2014/3/20
Y1 - 2014/3/20
N2 - The midbrain periaqueductal gray (PAG) is an integrative neural site in regulating several physiological functions including cardiovascular activities driven by sympathetic nervous system. Specifically, activation of the dorsolateral PAG (dl-PAG) leads to increases in sympathetic nervous activity and arterial blood pressure. Our recent studies demonstrated that angiotensin-(1-7) [Ang-(1-7)] plays an inhibitory role in neuronal activity of the dl-PAG via a Mas-R [Ang-(1-7) receptor] and neuronal NO dependent signaling pathway (Mas-R-nNOS). Because sympathetic nervous activity is augmented in chronic heart failure (HF), the present study was to determine (1) the levels of Ang-(1-7) and Mas-R-nNOS expression within the dl-PAG of control rats and rats with HF and (2) the role for Ang-(1-7) in modulating activity of dl-PAG neurons in both groups. Results showed that chronic HF decreased the levels of Ang-(1-7) and attenuated Mas-R-nNOS pathways. Also, we demonstrated that the discharge rates of dl-PAG neurons of HF rats (5.52. ±. 0.52. Hz, n= 21, P<. 0.05 vs. control) were augmented as compared with control rats (4.03. ±. 0.39. Hz, n= 28) and an inhibitory role played by Ang-(1-7) in neuronal activity of the dl-PAG was significantly decreased in HF (51. ±. 6%, P<. 0.05 vs. control) as compared with controls (72. ±. 8%). Our findings suggest that the inhibitory effects of Ang-(1-7) on dl-PAG neurons are impaired in HF, likely due to attenuated Mas-R-nNOS signaling pathways.
AB - The midbrain periaqueductal gray (PAG) is an integrative neural site in regulating several physiological functions including cardiovascular activities driven by sympathetic nervous system. Specifically, activation of the dorsolateral PAG (dl-PAG) leads to increases in sympathetic nervous activity and arterial blood pressure. Our recent studies demonstrated that angiotensin-(1-7) [Ang-(1-7)] plays an inhibitory role in neuronal activity of the dl-PAG via a Mas-R [Ang-(1-7) receptor] and neuronal NO dependent signaling pathway (Mas-R-nNOS). Because sympathetic nervous activity is augmented in chronic heart failure (HF), the present study was to determine (1) the levels of Ang-(1-7) and Mas-R-nNOS expression within the dl-PAG of control rats and rats with HF and (2) the role for Ang-(1-7) in modulating activity of dl-PAG neurons in both groups. Results showed that chronic HF decreased the levels of Ang-(1-7) and attenuated Mas-R-nNOS pathways. Also, we demonstrated that the discharge rates of dl-PAG neurons of HF rats (5.52. ±. 0.52. Hz, n= 21, P<. 0.05 vs. control) were augmented as compared with control rats (4.03. ±. 0.39. Hz, n= 28) and an inhibitory role played by Ang-(1-7) in neuronal activity of the dl-PAG was significantly decreased in HF (51. ±. 6%, P<. 0.05 vs. control) as compared with controls (72. ±. 8%). Our findings suggest that the inhibitory effects of Ang-(1-7) on dl-PAG neurons are impaired in HF, likely due to attenuated Mas-R-nNOS signaling pathways.
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U2 - 10.1016/j.neulet.2014.01.025
DO - 10.1016/j.neulet.2014.01.025
M3 - Article
C2 - 24472567
AN - SCOPUS:84893702997
SN - 0304-3940
VL - 563
SP - 6
EP - 11
JO - Neuroscience letters
JF - Neuroscience letters
ER -