title: Decreased adrenoceptor stimulation in heart failure rats reduces NGF expression by cardiac parasympathetic neurons.
abstract: Postganglionic cardiac parasympathetic and sympathetic nerves are physically proximate in atrial cardiac tissue allowing reciprocal inhibition of neurotransmitter release, depending on demands from central cardiovascular centers or reflex pathways. Parasympathetic cardiac ganglion (CG) neurons synthesize and release the sympathetic neurotrophin nerve growth factor (NGF), which may serve to maintain these close connections. In this study we investigated whether NGF synthesis by CG neurons is altered in heart failure, and whether norepinephrine from sympathetic neurons promotes NGF synthesis. NGF and proNGF immunoreactivity in CG neurons in heart failure rats following chronic coronary artery ligation was investigated. NGF immunoreactivity was decreased significantly in heart failure rats compared to sham-operated animals, whereas proNGF expression was unchanged. Changes in neurochemistry of CG neurons included attenuated expression of the cholinergic marker vesicular acetylcholine transporter, and increased expression of the neuropeptide vasoactive intestinal polypeptide. To further investigate norepinephrine's role in promoting NGF synthesis, we cultured CG neurons treated with adrenergic receptor (AR) agonists. An 82% increase in NGF mRNA levels was detected after 1h of isoproterenol (β-AR agonist) treatment, which increased an additional 22% at 24h. Antagonist treatment blocked isoproterenol-induced increases in NGF transcripts. In contrast, the α-AR agonist phenylephrine did not alter NGF mRNA expression. These results are consistent with β-AR mediated maintenance of NGF synthesis in CG neurons. In heart failure, a decrease in NGF synthesis by CG neurons may potentially contribute to reduced connections with adjacent sympathetic nerves.
authors: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, United States. Electronic address: hasan@ohsu.edu.
authors: Wohaib
authors: W
authors: Hasan
authors: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, United States.
authors: Peter G
authors: PG
authors: Smith
mesh_terms: D018674:Adrenergic Antagonists / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D006321:Heart / Q000294:innervation*; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D020932:Nerve Growth Factor / Q000096:biosynthesis*; D009414:Nerve Growth Factors / Q000096:biosynthesis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D011498:Protein Precursors / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000378:metabolism*; D013997:Time Factors; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism
chemical_list: D018674:Adrenergic Antagonists; D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D009414:Nerve Growth Factors; D011498:Protein Precursors; D012333:RNA, Messenger; D011941:Receptors, Adrenergic; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; C514218:pro-nerve growth factor, rat; D010656:Phenylephrine; D014660:Vasoactive Intestinal Peptide; D020932:Nerve Growth Factor; D007545:Isoproterenol
keywords: Adrenergic receptor; Autonomic; Cardiac ganglion; Heart failure; Nerve growth factor; Parasympathetic