Angiotensin-(1-7) inhibits neuronal activity of dorsolateral periaqueductal gray via a nitric oxide pathway.
The midbrain periaqueductal gray (PAG) is a neural site for several physiological functions related to cardiovascular regulation, pain modulation and behavioral reactions. Recently, angiotensin-(1-7) [Ang-(1-7)] has been considered as an important biologically active component of the renin-angiotensin system in the CNS. The purpose of this study was to determine (1) existence of Ang-(1-7) receptor, Mas-R, within the dorsolateral PAG (dl-PAG), (2) the role for Ang-(1-7) in modulating activity of dl-PAG neurons, and (3) the mechanisms by which Ang-(1-7) plays a regulatory role. Western blot analysis showed that Mas-R appears within the dl-PAG. Whole cell patch-clamp recording demonstrated that the discharge rates of dl-PAG neurons were decreased from 4.35±0.32 Hz of control to 1.06±0.34 Hz (P<0.05, vs. control) by 100 nM of Ang-(1-7). With pretreatment of A-779, a Mas-R inhibitor, the discharge rate was 4.66±0.62 Hz (P>0.05, vs. control) during infusion of Ang-(1-7). Additionally, neuronal nitric oxide synthase (nNOS) was largely localized within the dl-PAG among the three isoforms. The effects of Ang-(1-7) on neuronal activity of the PAG were attenuated in the presence of S-methyl-L-thiocitrulline (SMTC), a nNOS inhibitor. The discharge rates were 4.21±0.39 Hz in control and 4.09±0⋅47 Hz (P>0.05, vs. control) when Ang-(1-7) was applied with pretreatment of SMTC. Those findings suggest that Ang-(1-7) plays an inhibitory role in the dl-PAG via a NO dependent signaling pathway. This offers the basis for the physiological role of Ang-(1-7) and Mas R in the regulation of various functions in the CNS.
The First Hospital of Jilin University, Norman Bethune College of Medicine, Jilin University, Changchun 130021, China.
Jihong
J
Xing
Jian
J
Kong
Jian
J
Lu
Jianhua
J
Li
D000803:Angiotensin I / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D002956:Citrulline / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology* / Q000502:physiology; D010487:Periaqueductal Gray / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D002956:Citrulline; D009569:Nitric Oxide; D000803:Angiotensin I; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D013890:Thiourea; C118790:angiotensin I (1-7); C086717:S-methylthiocitrulline