EFFECT OF ANGIOTENSIN II ON A SPINAL NOCICEPTIVE REFLEX IN THE RAT: RECEPTOR AND MECHANISM OF ACTION

• Published in: Life sciences (1973) Vol. 61; no. 5; pp. 503 - 513
• Main Authors: Toma, Nicola, Sgambato, Véronique, Couture, Réjean
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 1997
• Subjects: angiotensin II; Angiotensin II - administration & dosage; Angiotensin II - analogs & derivatives; Angiotensin II - antagonists & inhibitors; Angiotensin II - pharmacology; Angiotensin Receptor Antagonists; Animals; AT 1 receptor; Biphenyl Compounds - pharmacology; Dose-Response Relationship, Drug; Drug Interactions; Hot Temperature; Imidazoles - pharmacology; Injections, Spinal; Losartan; Male; Naloxone - antagonists & inhibitors; Naloxone - pharmacology; Neurokinin A - analogs & derivatives; Neurokinin A - pharmacology; Neurokinin B - analogs & derivatives; Neurokinin B - pharmacology; nociception; Nociceptors - drug effects; opioids; Peptide Fragments - pharmacology; Rats; Rats, Sprague-Dawley; Reflex - drug effects; spinal cord; Spinal Cord - drug effects; Spinal Cord - metabolism; Substance P - pharmacology; tachykinin; Tetrazoles - pharmacology; AT 1 receptor; nociception; spinal cord; angiotensin II; opioids; tachykinin
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(97)00410-4

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 AT 1 receptor) or [Sar [1], Leu [8]] 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 μg) completely inhibited the response to 6.5 nmol Ang II. Losartan (65 pmol) and [Sar [1], Leu [8]] Ang II (6.5 nmol) blocked the antinociception induced by Ang II but were inactive against [MePhe [7]]neurokinin B. Furthermore, losartan failed to affect the hyperalgesic responses induced by substance P (6.5 nmol) or [β-Ala [8]]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 AT 1 receptor in the rat spinal cord.