title: Hydralazine administration activates sympathetic preganglionic neurons whose activity mobilizes glucose and increases cardiovascular function.
abstract: Hypotensive drugs have been used to identify central neurons that mediate compensatory baroreceptor reflex responses. Such drugs also increase blood glucose. Our aim was to identify the neurochemical phenotypes of sympathetic preganglionic neurons (SPN) and adrenal chromaffin cells activated following hydralazine (HDZ; 10mg/kg) administration in rats, and utilize this and SPN target organ destination to ascribe their function as cardiovascular or glucose regulating. Blood glucose was measured and adrenal chromaffin cell activation was assessed using c-Fos immunoreactivity (-ir) and phosphorylation of tyrosine hydroxylase, respectively. The activation and neurochemical phenotype of SPN innervating the adrenal glands and celiac ganglia were determined using the retrograde tracer cholera toxin B subunit, in combination with in situ hybridization and immunohistochemistry. Blood glucose was elevated at multiple time points following HDZ administration but little evidence of chromaffin cell activation was seen suggesting non-adrenal mechanisms contribute to the sustained hyperglycemia. 16±0.1% of T4-T11 SPN contained c-Fos and of these: 24.3±1.4% projected to adrenal glands and 29±5.5% projected to celiac ganglia with the rest innervating other targets. 62.8±1.4% of SPN innervating adrenal glands were activated and 29.9±3.3% expressed PPE mRNA whereas 53.2±8.6% of SPN innervating celiac ganglia were activated and 31.2±8.8% expressed PPE mRNA. CART-ir SPN innervating each target were also activated and did not co-express PPE mRNA. Neurochemical coding reveals that HDZ administration activates both PPE+SPN, whose activity increase glucose mobilization causing hyperglycemia, as well as CART+SPN whose activity drive vasomotor responses mediated by baroreceptor unloading to raise vascular tone and heart rate.
authors: The Australian School of Advanced Medicine, 2 Technology Place, Macquarie University, Sydney 2109, NSW, Australia.
authors: Lindsay M
authors: LM
authors: Parker
authors: The Australian School of Advanced Medicine, 2 Technology Place, Macquarie University, Sydney 2109, NSW, Australia; Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
authors: Hanafi A
authors: HA
authors: Damanhuri
authors: The Australian School of Advanced Medicine, 2 Technology Place, Macquarie University, Sydney 2109, NSW, Australia.
authors: Sophie P S
authors: SP
authors: Fletcher
authors: The Australian School of Advanced Medicine, 2 Technology Place, Macquarie University, Sydney 2109, NSW, Australia. Electronic address: ann.goodchild@mq.edu.au.
authors: Ann K
authors: AK
authors: Goodchild
mesh_terms: D000313:Adrenal Medulla / Q000294:innervation; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001339:Autonomic Fibers, Preganglionic / Q000187:drug effects* / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D019439:Chromaffin Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006830:Hydralazine / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000959:Antihypertensive Agents; D001786:Blood Glucose; D016760:Proto-Oncogene Proteins c-fos; D006830:Hydralazine; D005947:Glucose
keywords: Glucose mobilization; Hydralazine; Hypotension; Neurochemical phenotype; Sympathetic preganglionic neurons