title: Medullary GABAergic mechanisms contribute to electroacupuncture modulation of cardiovascular depressor responses during gastric distention in rats.
abstract: Electroacupuncture (EA) at P5-P6 acupoints overlying the median nerves typically reduces sympathoexcitatory blood pressure (BP) reflex responses in eucapnic rats. Gastric distention in hypercapnic acidotic rats, by activating both vagal and sympathetic afferents, decreases heart rate (HR) and BP through actions in the rostral ventrolateral medulla (rVLM) and nucleus ambiguus (NAmb), leading to sympathetic withdrawal and parasympathetic activation, respectively. A GABAA mechanism in the rVLM mediates the decreased sympathetic outflow. The present study investigated the hypothesis that EA modulates gastric distention-induced hemodynamic depressor and bradycardia responses through nuclei that process parasympathetic and sympathetic outflow. Anesthetized hypercapnic acidotic rats manifested repeatable decreases in BP and HR with gastric distention every 10 min. Bilateral EA at P5-P6 for 30 min reversed the hypotensive response from -26 ± 3 to -6 ± 1 mmHg and the bradycardia from -35 ± 11 to -10 ± 3 beats/min for a period that lasted more than 70 min. Immunohistochemistry and in situ hybridization to detect c-Fos protein and GAD 67 mRNA expression showed that GABAergic caudal ventral lateral medulla (cVLM) neurons were activated by EA. Glutamatergic antagonism of cVLM neurons with kynurenic acid reversed the actions of EA. Gabazine used to block GABAA receptors microinjected into the rVLM or cVLM reversed EA's action on both the reflex depressor and bradycardia responses. EA modulation of the decreased HR was inhibited by microinjection of gabazine into the NAmb. Thus, EA through GABAA receptor mechanisms in the rVLM, cVLM, and NAmb modulates gastric distention-induced reflex sympathoinhibition and vagal excitation.
authors.affiliation: Susan Samueli Center for Integrative Medicine, Department of Medicine, School of Medicine, University of California, Irvine, CA 92697, USA. stjenalo@uci.edu
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Tjen-A-Looi
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Guo
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: John C
authors.initials: JC
authors.lastname: Longhurst
mesh_terms: D000142:Acidosis, Respiratory / Q000503:physiopathology; D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology; D001919:Bradycardia / Q000503:physiopathology; D002319:Cardiovascular System / Q000294:innervation*; D015671:Electroacupuncture / Q000379:methods*; D018756:GABA Antagonists / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000235:genetics; D018698:Glutamic Acid / Q000502:physiology; D006935:Hypercapnia / Q000503:physiopathology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D009433:Neural Inhibition / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology; D012018:Reflex / Q000502:physiology; D013270:Stomach / Q000294:innervation* / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D018756:GABA Antagonists; D016760:Proto-Oncogene Proteins c-fos; D011724:Pyridazines; D011963:Receptors, GABA-A; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C049853:gabazine; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1