title: Effect of barodenervation on cardiovascular responses elicited from the hypothalamic arcuate nucleus of the rat.
abstract: We have previously reported that chemical stimulation of the hypothalamic arcuate nucleus (ARCN) in the rat elicited increases as well as decreases in blood pressure (BP) and sympathetic nerve activity (SNA). The type of response elicited from the ARCN (i.e., increase or decrease in BP and SNA) depended on the level of baroreceptor activity which, in turn, was determined by baseline BP in rats with intact baroreceptors. Based on this information, it was hypothesized that baroreceptor unloading may play a role in the type of response elicited from the ARCN. Therefore, the effect of barodenervation on the ARCN-induced cardiovascular and sympathetic responses and the neurotransmitters in the hypothalamic paraventricular nucleus (PVN) mediating the excitatory responses elicited from the ARCN were investigated in urethane-anesthetized adult male Wistar rats. Bilateral barodenervation converted decreases in mean arterial pressure (MAP) and greater splanchnic nerve activity (GSNA) elicited by chemical stimulation of the ARCN with microinjections of N-methyl-D-aspartic acid to increases in MAP and GSNA and exaggerated the increases in heart rate (HR). Combined microinjections of NBQX and D-AP7 (ionotropic glutamate receptor antagonists) into the PVN in barodenervated rats converted increases in MAP and GSNA elicited by the ARCN stimulation to decreases in MAP and GSNA and attenuated increases in HR. Microinjections of SHU9119 (a melanocortin 3/4 receptor antagonist) into the PVN in barodenervated rats attenuated increases in MAP, GSNA and HR elicited by the ARCN stimulation. ARCN neurons projecting to the PVN were immunoreactive for proopiomelanocortin, alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH). It was concluded that increases in MAP and GSNA and exaggeration of tachycardia elicited by the ARCN stimulation in barodenervated rats may be mediated via release of alpha-MSH and/or ACTH and glutamate from the ARCN neurons projecting to the PVN.
authors.affiliation: Department of Neurological Surgery, University of Medicine and Dentistry of New Jersey- New Jersey Medical School, Newark, New Jersey, United States of America.
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: D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002319:Cardiovascular System / Q000187:drug effects / Q000294:innervation*; D003714:Denervation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D011311:Pressoreceptors / Q000503:physiopathology*; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018043:Receptors, Corticotropin / Q000037:antagonists & inhibitors; D013153:Splanchnic Nerves / Q000187:drug effects / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D000521:alpha-MSH
chemical_list: D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018043:Receptors, Corticotropin; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C103272:SHU 9119; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; D015763:2-Amino-5-phosphonovalerate; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones; C031231:2-amino-7-phosphonoheptanoic acid