Angiotensin (5–8) modulates nociception at the rat periaqueductal gray via the NO–sGC pathway and an endogenous opioid

• Published in: Neuroscience Vol. 231; pp. 315 - 327
• Main Authors: Guethe, L.M, Pelegrini-da-Silva, A, Borelli, K.G, Juliano, M.A, Pelosi, G.G, Pesquero, J.B, Silva, C.L.M, Corrêa, F.M.A, Murad, F, Prado, W.A, Martins, A.R
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 12.02.2013
• Subjects: angiotensin (5–8); Angiotensin I - pharmacology; Angiotensin Receptor Antagonists - pharmacology; Animals; antinociception; Aorta - drug effects; Dose-Response Relationship, Drug; Guanylate Cyclase - metabolism; Heart Rate - physiology; incision allodynia model; Male; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Neurology; Nitric Oxide - metabolism; Nociception - drug effects; Opioid Peptides - antagonists & inhibitors; Opioid Peptides - metabolism; pain; Peptide Fragments - pharmacology; Periaqueductal Gray - drug effects; periaqueductal gray matter; Rats; Rats, Wistar; Receptors, Cytoplasmic and Nuclear - metabolism; Saralasin - pharmacology; Signal Transduction - drug effects; Soluble Guanylyl Cyclase; tail-flick test; Teprotide - pharmacology; NO; DMSO; dimethylsulfoxide; N ω-propyl- l-arginine; RAS; HR; tail-flick test; phosphate-buffered saline; ventrolateral periaqueductal gray matter; renin–angiotensin system; sGC; NPLA; analysis of variance; soluble guanylyl cyclase; ANOVA; angiotensin (5–8); ODQ; incision allodynia model; AA; PBS; heart rate; nitric oxide; pain; antinociception; Angs; mean arterial pressure; neuronal nitric oxide synthase; 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one; Ang receptor; opioid receptor; opioid-R; vlPAG; AT; Ang type; Ang type receptor; nNOS; Ang-R; periaqueductal gray matter; angiotensins; MAP; antinociceptive activity; ATR
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2012.11.048

Highlights ► Ang (5–8) injection into PAG selectively elicits Ang-R-mediated antinociception. ► The PAG both synthesizes and inactivates Ang (5–8). ► Ang (5–8) modulates antinociception via NO–sGC pathway and opioid. ► Ang (5–8) antinociception is 74-fold more potent than that of morphine. ► Ang (5–8) can be a leading compound to develop potent and selective analgesic drugs.