Antihyperalgesic Effect of an Angiotensin 1-7 Structural Analogue in Rats

Abstract

Angiotensin 1-7 (Ang-(1-7)) is a key endogenous heptapeptide with an active role in the Renin-Angiotensin System. It exerts vasodilatory, antiproliferative, antioxidant, anti-inflammatory, and peripheral antinociceptive effects, binding to a specific receptor (MasR). Previous data have shown an antinociceptive effect of Ang-(1-7) with a putative Mas receptor-dependent mechanism, which highlights its analgesic potential and stimulates the synthesis of its new peptide analogues with improved properties. Our preliminary study showed that some newly synthesized Ang-(1-7) analogues exhibit antinociceptive effects after a single intraperitoneal injection in mice subjected to the formalin test. The present study aimed to examine the effects of sub-chronic local (intraplantar) administration of a new Ang-(1-7) analogue, Ang-P2, at different doses in a rat model of inflammatory hyperalgesia. The hyperalgesia was induced by an intraplantar injection of γ-Carrageenan in adult male Wistar rats. Ang-P2 was administered intraplantarly, in the same paw, at three different doses before the Carrageenan injection, and then daily (for 7 days), before the measurement of pain sensitivity. The mechanical pain thresholds were measured via an electronic Von Frey analgesiometer (Ugo Basile) and further statistically analyzed.  Sub-chronic injected indomethacin was used as a reference drug.

Ang-P2 at a dose of 2.5 μg/10 μl significantly alleviated Carrageenan-induced hyperalgesia during the first 4 days of treatment, while the lower and higher doses were ineffective. The antihyperalgesic effect was comparable to that of the reference drug indomethacin. We can conclude that sub-chronic local administration of this newly synthesized Ang-(1-7) analogue produces a dose-dependent effect against the inflammatory mechanical hyperalgesia. Further studies are planned to elucidate its mechanism of action.