Participation of Nitric Oxide and GABA at the Nucleus Tractus Solitarii in Cardiovascular Effects induced by Orexin in the Rat

• Main Authors: Yu-cheng Chuang, 莊育姃
• Other Authors: Cheng-Dean Shih
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/53635688629385186255

碩士 === 大仁科技大學 === 製藥科技研究所 === 94 === Orexins include orexin (OX)-A and OX-B, which are 33- and 28-amino acid peptides, respectively, proteolytically derived from the same precursor protein. They were recently discovered in the hypothalamus. The present study investigated the cardiovascular effects of OX-A and OX-B in the nucleus tractus solitarii (NTS) and delineated the roles played by nitric oxide (NO) and GABA. In Sprague-Dawley rats maintained under propofol anesthesia, bilateral microinjection of OX-A or OX-B into the NTS promoted paradoxical cardiovascular effects in a dose-dependent manner. At higher doses (20-200 pmol), OX-A or OX-B promoted cardiovascular excitation of increased systemic arterial pressure (SAP), heart rate (HR), or power density of the vasomotor components of SAP signals. At a lower dose (5 pmol), these two compounds elicited cardiovascular depression. Both effects were abolished by co-injection of an OX-A receptor antagonist, SB-334867 (0.75 nmol) or the OX-B receptor antiserum (1:20). In addition, the vasodepressor effects of OX-A or OX-B (5 pmol) in the NTS were abolished by a nonselective NO synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester hydrochloride (5 nmol), a selective neuronal NOS (nNOS) inhibitor, 7-nitroindazole (2.5 pmol) or a soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (250 pmol). Co-treatment with inducible NOS (iNOS) inhibitor, S-Methylisothiourea (500 pmol) or endothelial NOS (eNOS) inhibitor, L-N5-(1-Iminoethyl)-ornithine dihydrochloride (100 pmol) did not affect these effects. The OX-induced cardiovascular inhibitory (200 pmol) were reversed by co-administration with GABAA or GABAB receptor antagonist, bicuculline methiodine (10 pmol) or 2-hydroxy saclofen (100 pmol). Our results indicate that the OX elicited paradoxical cardiovascular effects via OX receptor-mediated mechanisms. The cardiovascular excitatory effects were mediated by activation of GABAA or GABAB receptors, and the cardiovascular depressive effects were induced by the nNOS-derived NO and activation of sGC-associated signaling pathway.