title: Melanocortin 3/4 receptors in paraventricular nucleus modulate sympathetic outflow and blood pressure.
abstract: Central melanocortin 3/4 receptors (MC3/4Rs) are known to regulate energy balance. Activation of MC3/4Rs causes a greater increase in the firing activity of the PVN neurons in obese Zucker rats than in lean Zucker rats. The present study was undertaken to determine the roles of MC3/4Rs in the hypothalamic paraventricular nucleus (PVN) in modulating the sympathetic activity and blood pressure and its downstream pathway. Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anaesthetized rats. Microinjection of the MC3/4R agonist melanotan II (MTII) into the PVN increased the RSNA and MAP. The MC3/4R antagonist agouti-related peptide (AgRP) or SHU9119 decreased the RSNA and MAP, but the MC4R antagonist HS024 had no significant effect on the RSNA and MAP. The effects of MTII were abolished by pretreatment of the PVN with AgRP, SHU9119, the adenylate cyclase inhibitor SQ22536 or the protein kinase A inhibitor Rp-cAMP, and substantially attenuated by HS024. Microinjection of SQ22536 alone into the PVN had no significant effect on the RSNA and MAP, but Rp-cAMP caused significant decreases in the RSNA and MAP. Furthermore, MTII increased the cAMP level in the PVN. These results indicate that activation of MC3/4Rs in the PVN increases the sympathetic outflow and blood pressure via the cAMP-protein kinase A pathway. Melanocortin 3 receptors in the PVN may exert a tonic excitatory effect on sympathetic activity.
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Bai-Ping
authors.initials: BP
authors.lastname: Cui
authors.forename: Ling-Li
authors.initials: LL
authors.lastname: Zhang
authors.forename: Hai-Jian
authors.initials: HJ
authors.lastname: Sun
authors.forename: Tong-Yan
authors.initials: TY
authors.lastname: Liu
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Zhu
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D054369:Agouti-Related Protein / Q000008:administration & dosage; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000294:innervation*; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000008:administration & dosage; D008845:Microinjections; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000008:administration & dosage; D010456:Peptides, Cyclic / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4 / Q000378:metabolism*; D044101:Receptors, Melanocortin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015290:Second Messenger Systems; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors; D000521:alpha-MSH / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D054369:Agouti-Related Protein; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D047428:Protein Kinase Inhibitors; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D044101:Receptors, Melanocortin; D013873:Thionucleotides; C514973:melanocortin 3 receptor, rat; C079282:melanotan-II; C103272:SHU 9119; C017759:9-(tetrahydro-2-furyl)-adenine; D000521:alpha-MSH; D009074:Melanocyte-Stimulating Hormones; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D000225:Adenine