title: Cardiovascular responses to chemical stimulation of the hypothalamic arcuate nucleus in the rat: role of the hypothalamic paraventricular nucleus.
abstract: The mechanism of cardiovascular responses to chemical stimulation of the hypothalamic arcuate nucleus (ARCN) was studied in urethane-anesthetized adult male Wistar rats. At the baseline mean arterial pressure (BLMAP) close to normal, ARCN stimulation elicited decreases in MAP and sympathetic nerve activity (SNA). The decreases in MAP elicited by ARCN stimulation were attenuated by either gamma-aminobutyric acid (GABA), neuropeptide Y (NPY), or beta-endorphin receptor blockade in the ipsilateral hypothalamic paraventricular nucleus (PVN). Combined blockade of GABA-A, NPY1 and opioid receptors in the ipsilateral PVN converted the decreases in MAP and SNA to increases in these variables. Conversion of inhibitory effects on the MAP and SNA to excitatory effects following ARCN stimulation was also observed when the BLMAP was decreased to below normal levels by an infusion of sodium nitroprusside. The pressor and tachycardic responses to ARCN stimulation at below normal BLMAP were attenuated by blockade of melanocortin 3/4 (MC3/4) receptors in the ipsilateral PVN. Unilateral blockade of GABA-A receptors in the ARCN increased the BLMAP and heart rate (HR) revealing tonic inhibition of the excitatory neurons in the ARCN. ARCN stimulation elicited tachycardia regardless of the level of BLMAP. ARCN neurons projecting to the PVN were immunoreactive for glutamic acid decarboxylase 67 (GAD67), NPY, and beta-endorphin. These results indicated that: 1) at normal BLMAP, decreases in MAP and SNA induced by ARCN stimulation were mediated via GABA-A, NPY1 and opioid receptors in the PVN, 2) lowering of BLMAP converted decreases in MAP following ARCN stimulation to increases in MAP, and 3) at below normal BLMAP, increases in MAP and HR induced by ARCN stimulation were mediated via MC3/4 receptors in the PVN. These results provide a base for future studies to explore the role of ARCN in cardiovascular diseases.
authors.affiliation: Department of Neurological Surgery, University of Medicine and Dentistry of New Jersey- New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kawabe
authors.forename: Kazumi
authors.initials: K
authors.lastname: Kawabe
authors.forename: Hreday N
authors.initials: HN
authors.lastname: Sapru
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D062186:Arterial Pressure / Q000187:drug effects / Q000502:physiology; D002319:Cardiovascular System / Q000187:drug effects* / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009292:Narcotic Antagonists; D009478:Neuropeptide Y / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D044101:Receptors, Melanocortin / Q000037:antagonists & inhibitors / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D011957:Receptors, Opioid / Q000819:agonists / Q000378:metabolism; D013268:Stimulation, Chemical; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D001615:beta-Endorphin / Q000494:pharmacology
chemical_list: D009292:Narcotic Antagonists; D009478:Neuropeptide Y; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D011963:Receptors, GABA-A; D044101:Receptors, Melanocortin; D017476:Receptors, Neuropeptide Y; D011957:Receptors, Opioid; C514973:melanocortin 3 receptor, rat; D009599:Nitroprusside; D001615:beta-Endorphin; D016202:N-Methylaspartate; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1