The Effects of Central Angiotensin Ii and Its Specific Blockers on Nociception. Possible Interactions with Oxidative Stress Status Efekti Centralnog Angiotenzina Ii I Njegovih Specifi^nih Blokatora Na Nocicepciju. Mogu]e Interakcije Sa Statusom Oksidativnog Stresa

Ciobica Alin »Alexandru Ioan Cuza« University Dept. of Biology B dul Carol I, 11 700506, Iasi, Romania Tel :0040751218264; Fax 0040232201472 e-mail: alin.ciobicaauaic.ro 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 contro versial. Also, it seems that oxidative stress follows angio tensin 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 in tra cerebroventricular administration of losartan and PD123177 (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 behavio ral test for pain perception. We present here the analgesic effect of angiotensin II administration, as shown by in crea sed 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 la ten cy-time. Moreover, we demonstrated a significant correlation between the results of the nociceptive Kratak sadr`aj: Do sada je ve} pokazano da kompletan mo`dani renin–angiotenzin sistem (RAS) postoji zasebno od perifernog sistema i da je uklju~en u slo`ene funkcije kao {to su memorija, emocionalni odgovori i bol. [to se ti~e im plikacija angiotenzina II (glavnog bioaktivnog peptida RAS) u bolu, mada u ovoj oblasti istra`ivanja postoje mnoge studije, rezultati su ve}inom opre~ni. Tako|e, izgleda da infuziju angiotenzina II prati oksidativni stres, ali uloga receptora AT1 i AT2 jo{ nije razja{njena. U tom kontekstu hteli smo da prou~imo efekte centralnog RAS na nocicepciju preko intra cerebroventrikularne administracije lozartana i PD-123177 (antagonista za receptore AT1/AT2) kao i jednog ACE in hi bitora (kaptopril) i angiotenzina II kod pacova, koji su potom testirani metodom grejne plo~e, poznatim bihevioralnim testom za percepciju bola. Predstavljamo analgeti~ki efekat administracije angiotenzina II pokazan kroz pove}anu latenciju na grejnoj plo~i, kao i nociceptivni efekat blokatora angiotenzina II kao {to su antagonisti specifi~ni za AT1 i AT2 (lozartan i PD-123177) i ACE inhibitora (kaptopril), po{to je rezultat njihove administracije bila smanjena latencija. [ta vi{e, uo~ili smo zna~ajnu korelaciju izme|u rezultata nociceptivnog bihevioralnog testa i nivoa nekih od glavnih mar kera oksidativnog stresa. Na taj na~in obezbe|eni su novi