Decrease in arterial pressure induced by adrenomedullin in the hypothalamic paraventricular nucleus is mediated by nitric oxide and GABA.
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.
Xu
Yong
Y
Department of Cell Biology and Center for Neuroscience, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada T6G 2H7.
Krukoff
Teresa L
TL
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*
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