文摘
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 卤 0.52 Hz, n = 21, P < 0.05 vs. control) were augmented as compared with control rats (4.03 卤 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 卤 6%, P < 0.05 vs. control) as compared with controls (72 卤 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.
