title: Decrease in arterial pressure induced by adrenomedullin in the hypothalamic paraventricular nucleus is mediated by nitric oxide and GABA.
abstract: We tested the hypothesis that the decrease in arterial pressure induced by adrenomedullin (ADM) in the hypothalamic paraventricular nucleus (PVN) is mediated by nitric oxide (NO) and/or GABA. Unilateral microinjections of ADM into the PVN of anesthetized rats caused a significant decrease in mean arterial pressure (MAP). The ADM-induced decrease in MAP was significantly attenuated by pretreatment with N(psi)-nitro-L-arginine methyl ester (L-NAME, a non-selective NOS inhibitor), 7-nitroindazole sodium salt (7-NiNa, a selective neuronal NOS inhibitor), N5-(1-Iminoethyl)-L-ornithine (L-NIO, a selective endothelial NOS inhibitor) or bicuculline methiodide, but pretreatment with S-methylisothiourea (SMIT, a selective inducible NOS inhibitor) had no effect on this ADM-induced effect. In addition, coronal sections of rat brains were processed for combined NADPH-diaphorase (a marker of neuronal NOS-containing neurons) histochemistry and in situ hybridization for the receptor-activity-modifying protein 2 (a specific ADM receptor component). Double-labeled neurons were found in both parvocellular and magnocellular subdivisions of the PVN, confirming that NO-producing neurons in the PVN are capable of mediating ADM's effects. Thus, our data provide evidence that the ADM-induced decrease in MAP in the PVN is mediated by NO from neuronal and endothelial NOS, and by GABA.
authors.affiliation: Department of Cell Biology and Center for Neuroscience, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada T6G 2H7.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Krukoff
mesh_terms: D053607:Adrenomedullin; D000818:Animals; D019540:Area Under Curve; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017403:In Situ Hybridization; D007191:Indazoles / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D007550:Isothiuronium / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D009249:NADP / Q000378:metabolism; D009252:NADPH Dehydrogenase / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009952:Ornithine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D058261:Receptor Activity-Modifying Proteins; D012964:Sodium / Q000494:pharmacology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D007191:Indazoles; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010455:Peptides; D058261:Receptor Activity-Modifying Proteins; D053607:Adrenomedullin; D007550:Isothiuronium; D009569:Nitric Oxide; C065027:N(G)-iminoethylornithine; C017069:bicuculline methiodide; D009249:NADP; D005680:gamma-Aminobutyric Acid; D012964:Sodium; D009952:Ornithine; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase; C027744:S-methylisothiopseudouronium; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester; D001640:Bicuculline