Effect of angiotensin II on a spinal nociceptive reflex in the rat: receptor and mechanism of action.
The effect on thermonociceptive threshold of intrathecally (i.t.) administered angiotensin II (Ang II) was assessed in the rat tail-flick test. Rats were pretreated, 15 min earlier, with i.t. naloxone (opiate antagonist), losartan (Ang II selective antagonist at AT1 receptor) or [Sar1, Leu8] Ang II (non selective Ang II receptor antagonist) to define the mechanism of action and the nature of the receptor subtype. Ang II (0.65-6.5 nmol) induced antinociceptive effects that peaked at 1 min post-injection and returned to baseline after 5-10 min. Naloxone (10 microg) completely inhibited the response to 6.5 nmol Ang II. Losartan (65 pmol) and [Sar1, Leu8] Ang II (6.5 nmol) blocked the antinociception induced by Ang II but were inactive against [MePhe7]neurokinin B. Furthermore, losartan failed to affect the hyperalgesic responses induced by substance P (6.5 nmol) or [beta-Ala8]neurokinin A (6.5 nmol). This study provides the first functional evidence that Ang II inhibits the transmission of thermal nociceptive information through an endogenous opioid mechanism and the activation of an AT1 receptor in the rat spinal cord.
Toma
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Department of Physiology, Faculty of Medicine, Université de Montréal, Succursale Centre-Ville, Québec, Canada.
Sgambato
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Couture
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R
D000804:Angiotensin II / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006358:Hot Temperature; D007093:Imidazoles / Q000494:pharmacology; D007278:Injections, Spinal; D019808:Losartan; D008297:Male; D009270:Naloxone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D015287:Neurokinin B / Q000031:analogs & derivatives / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D010446:Peptide Fragments; D013777:Tetrazoles; C080394:neurokinin B, MePhe(7)-; D000804:Angiotensin II; C064218:neurokinin A (4-10), beta-Ala(8)-; D013373:Substance P; D009270:Naloxone; C009210:sarleucin; D015288:Neurokinin A; D015287:Neurokinin B; D019808:Losartan