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The injection of angiotensins (Ang) III and IV in the rat periaqueductal gray matter (PAG) elicits antinociception.
Rosa1, E.; Guethe1, L.M.; Pelegrini-da-Silva2, A.; Juliano3, M.A.; Prado4, W.A. and Martins4 A.R.
Department of Psychology and Education1, FFCLRP-USP; Department of Physiology2, FOP-UNICAMP; Department of Biophysics3, UNIFESP-EPM; Department of Pharmacology4, FMRPUSP.
Objective Pelegrini-da-Silva et al [Neuroscience (2005) 132: 453-463] have shown that endogenous Ang II elicits receptor-mediated antinociception upon injection into the PAG. There are evidences to support the notion that most of CNS effects elicited by Ang II injection are predominantly due to Ang III. In starting to address this issue, we have tested whether Ang III and IV can elicit antinociception upon injection into the PAG.
Materials and methods Male albino Wistar rats (160–180 g) were anesthetized with tribrome-ethanol (25 mg/kg, i.p.). A 23-gauge stainless steel guide cannula was implanted into the skull to lie 3.0 mm above the target site in the ventrolateral (vl) PAG. The stereotaxic coordinates (in mm) used were AP, 1.0-1.96 from the ear bars; L, -1.9 from the midline; and H, -6.0 from the skull surface, all taken from Paxinos and Watson's (1986) atlas. Drug or vehicle (0.25 ml) was microinjected intracerebrally using a glass needle (70–90 mm, o.d.). The injection procedure and the localization of the injection site were as described by Pelegrini-da-Silva et al (2005).
Results The injection of Ang III (0.05-1.6 nmol) and Ang IV (0.8 nmol) into the vlPAG elicited antinociception, as estimated using the tail flick test. Although a clear–cut dose response curve was not obtained, antinociception was clearly related to the Ang III dose since saline or low Ang III doses did not elicit antinociception. In addition, the antinociceptive effect of Ang III changed according to the AP coordinate, being apparently more intense at 1.36, 1.70 and 1.96 mm.
Conclusions Ang III and IV elicited intense antinociception upon their injection into the vlPAG. This effect appears to be strongest at the rostral vlPAG region. Whether this effect is intrinsic to Ang III and/or IV or to a shorter Ang-peptide is currently being analyzed.
Supported by FAPESP, FAEPA and CNPq.
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