title: High plasma norepinephrine attenuates the dynamic heart rate response to vagal stimulation.
abstract: To better understand the pathophysiological significance of high plasma norepinephrine (NE) concentration in regulating heart rate (HR), we examined the interactions between high plasma NE and dynamic vagal control of HR. In anesthetized rabbits with sinoaortic denervation and vagotomy, using a binary white noise sequence (0-10 Hz) for 10 min, we stimulated the right vagus and estimated the transfer function from vagal stimulation to HR response. The transfer function approximated a first-order low-pass filter with pure delay. Infusion of NE (100 microg. kg(-1) x h(-1) iv) attenuated the dynamic gain from 6.2 +/- 0.8 to 3.9 +/- 1.2 beats x min(-1) x Hz(-1) (n = 7, P < 0.05) without affecting the corner frequency or pure delay. Simultaneous intravenous administration of phentolamine (1 mg x kg(-1) x h(-1)) and NE (100 microg x kg(-1) x h(-1)) abolished the inhibitory effect of NE on the dynamic gain (6.3 +/- 0.8 vs. 6.4 +/- 1.3 beats x min(-1) x Hz(-1), not significant, n = 7). The inhibitory effect of NE at infusion rates of 10, 50, and 100 microg x kg(-1) x h(-1) on dynamic vagal control of HR was dose-dependent (n = 5). In conclusion, high plasma NE attenuated the dynamic HR response to vagal stimulation, probably via activation of alpha-adrenergic receptors on the preganglionic and/or postganglionic cardiac vagal nerve terminals.
authors.affiliation: Department of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan. miyamoto@res.ncvc.go.jp
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Toru
authors.initials: T
authors.lastname: Kawada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takaki
authors.forename: Masashi
authors.initials: M
authors.lastname: Inagaki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Yanagiya
authors.forename: Yintie
authors.initials: Y
authors.lastname: Jin
authors.forename: Masaru
authors.initials: M
authors.lastname: Sugimachi
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000465:Algorithms; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006339:Heart Rate / Q000502:physiology*; D007262:Infusions, Intravenous; D009638:Norepinephrine / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011817:Rabbits; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D009638:Norepinephrine; D010646:Phentolamine