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Summary 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 AT1 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 in creased latency-time in the hot-plate, as well as a nociceptive effect of angiotensin II blockers like AT1 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 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. Kratak sadržaj Do sada je već pokazano da kompletan moždani renin-angiotenzin sistem (RAS) postoji zasebno od perifernog sistema i da je uključen u složene funkcije kao što su memorija, emocionalni odgovori i bol. Sto se tiče implikacija angiotenzina II (glavnog bioaktivnog peptida RAS) u bolu, mada u ovoj oblasti istraživanja postoje mnoge studije, rezultati su većinom oprečni. Takođe, izgleda da infuziju angiotenzina II prati oksidativni stres, ali uloga receptora ATI i AT2 još nije razjašnjena. U tom kontekstu hteli smo da proučimo efekte centralnog RAS na nocicepciju preko intracerebroventrikularne administracije lozartana i PD-123177 (antagonista za receptore AT1/AT2) kao i jednog ACE inhibitora (kaptopril) i angiotenzina II kod pacova, koji su potom testirani metodom grejne ploče, poznatim bihevioralnim testom za percepciju bola. Predstavljamo analgetički efekat administracije angiotenzina II pokazan kroz povećanu latenciju na grejnoj ploči, kao i nociceptivni efekat blokatora angiotenzina II kao što su antagonisti specifični za ATI i AT2 (lozartan i PD-123177) i ACE inhibitora (kaptopril), pošto je rezultat njihove administracije bila smanjena latencija. Staviše, uočili smo značajnu korelaciju između rezultata nociceptivnog bihevioralnog testa i nivoa nekih od glavnih markera oksidativnog stresa. Na taj način obezbeđeni su novi dokazi u korist analgetičkog efekta administracije Ang II, kao i nociceptivnog efekta blokatora Ang II. Uz to, predstavljena je značajna korelacija između nocicepcije i oksidativnog stresa izazvanog angiotenzinom II.

journal of medical biochemistry

The Effects of Central Angiotensin II and Its Specific Blockers on Nociception. Possible Interactions with Oxidative Stress Status / Efekti Centralnog Angiotenzina II I Njegovih Specifičnih Blokatora Na Nocicepciju. Moguće Interakcije Sa Statusom Oksidativnog Stresa