The effects of central angiotensin II and its specific blockers on nociception: Possible interactions with oxidative stress status

It has already been demonstrated that a complete brain renin angiotensin system (RAS) exists distinctly separate from the peripheral system and is implicated in complex functions such as memory, emotional responses and pain. Regarding the implications of angiotensin II (the main bioactive peptide of RAS) in pain, although there are many studies in this area of research, most of the results are controversial. Also, it seems that oxidative stress follows angiotensin II infusion, but the role of ATI vs. AT2 receptors is not well established. In this context, we were interested in studying the effects of central RAS on nociception, through the intracerebroventricular administration of losartan and PD- 123177 (antagonists for the AT1/AT2 receptors), as well as an ACE inhibitor (captopril) and also angiotensin II in rats, which were subsequently tested using the hot-plate task, a well-known behavioral test for pain perception. We present here the analgesic effect of angiotensin II administration, as shown by increased latency-time in the hot-plate, as well as a nociceptive effect of angiotensin II blockers like ATI and AT2 specific antagonists (losartan and PD-123177) and an ACE inhibitor (captopril), as their administration resulted in decreased latency-time. Moreover, we demonstrated a signif­icant correlation between the results of the nociceptive The discovery that all components of the renin- angiotensin system (RAS) are present in the brain led investigators to postulate the existence of a local brain RAS (1). In this way, it has already been demonstrated that a complete brain RAS exists that is distinctly separate from the peripheral system and comprises all necessary precursors and enzymes required for the formation and metabolism of the biologically active forms of angiotensins (2).behavioral task and the levels of some main oxidative stress markers. This provides additional evidence for an analgesic effect of Ang II administration, as well as for a nociceptive effect of Ang II blockers. Moreover, a significant correlation between the nociception and angiotensin II-induced oxidative stress is presented.