title: Acute adenosine increases cardiac vagal and reduces sympathetic efferent nerve activities in rats.
abstract: Adenosine is the first drug of choice in the treatment of supraventricular arrhythmias. While the effects of adenosine on sympathetic nerve activity (SNA) have been investigated, no information is available on the effects on cardiac vagal nerve activity (VNA). We assessed in rats the responses of cardiac VNA, SNA and cardiovascular variables to intravenous bolus administration of adenosine. In 34 urethane-anaesthetized rats, cardiac VNA or cervical preganglionic sympathetic fibres were recorded together with ECG, arterial pressure and ventilation, before and after administration of three doses of adenosine (100, 500 and 1000 μg kg(-1)). The effects of adenosine were also assessed in isolated perfused hearts (n = 5). Adenosine induced marked bradycardia and hypotension, associated with a significant dose-dependent increase in VNA (+204 ± 56%, P < 0.01; +275 ± 120%, P < 0.01; and +372 ± 78%, P < 0.01, for the three doses, respectively; n = 7). Muscarinic blockade by atropine (5 mg kg(-1), i.v.) significantly blunted the adenosine-induced bradycardia (-56.0 ± 4.5%, P < 0.05; -86.2 ± 10.5%, P < 0.01; and -34.3 ± 9.7%, P < 0.01, respectively). Likewise, adenosine-induced bradycardia was markedly less in isolated heart preparations. Previous barodenervation did not modify the effects of adenosine on VNA. On the SNA side, adenosine administration was associated with a dose-dependent biphasic response, including overactivation in the first few seconds followed by a later profound SNA reduction. Earliest sympathetic activation was abolished by barodenervation, while subsequent sympathetic withdrawal was affected neither by baro- nor by chemodenervation. This is the first demonstration that acute adenosine is able to activate cardiac VNA, possibly through a central action. This increase in vagal outflow could make an important contribution to the antiarrhythmic action of this substance.
authors.affiliation: Department of Clinical Sciences, University of Milan, Internal Medicine II, L. Sacco Hospital, Milan, Italy.
authors.forename: Valdo Jose Dias
authors.initials: VJ
authors.lastname: da Silva
authors.forename: Tomaso
authors.initials: T
authors.lastname: Gnecchi-Ruscone
authors.forename: Valentina
authors.initials: V
authors.lastname: Bellina
authors.forename: Mauro
authors.initials: M
authors.lastname: Oliveira
authors.forename: Leonardo
authors.initials: L
authors.lastname: Maciel
authors.forename: Antonio Carlos Campos
authors.initials: AC
authors.lastname: de Carvalho
authors.forename: Helio Cesar
authors.initials: HC
authors.lastname: Salgado
authors.forename: Cassia M
authors.initials: CM
authors.lastname: Bergamaschi
authors.forename: Eleonora
authors.initials: E
authors.lastname: Tobaldini
authors.forename: Alberto
authors.initials: A
authors.lastname: Porta
authors.forename: Nicola
authors.initials: N
authors.lastname: Montano
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000503:physiopathology; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001919:Bradycardia / Q000188:drug therapy / Q000503:physiopathology; D002319:Cardiovascular System / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology; D006321:Heart / Q000187:drug effects* / Q000294:innervation* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D007022:Hypotension / Q000188:drug therapy / Q000503:physiopathology; D009476:Neurons, Efferent / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology
chemical_list: D000889:Anti-Arrhythmia Agents; D001285:Atropine; D000241:Adenosine