Endogenous adenosine enhances vagal negative chronotropic effect during hypoxia in the anaesthetised rabbit.
OBJECTIVE
Hypoxia potentiates the negative chronotropic effect of efferent vagal stimulation. A similar potentiation is evoked by exogenous adenosine. The aim of this study was to verify whether vagal potentiation during hypoxia is caused by endogenous adenosine.


METHODS
In anaesthetised rabbits the peripheral end of the right vagus was stimulated once every 20 s for 1 s, during normoxia and during systemic hypoxia, before and after adenosine receptor blockade. Hypoxia was induced by lowering oxygen content of the inspired air for 6 min.


METHODS
12 rabbits were anaesthetised with chloralose (50 mg.kg-1, intravenously) and halothane (0.3 vol%) and artificially ventilated. Reflex influences on heart rate were minimised by bilateral cervical vagotomy and administration of atenolol (1 mg.kg-1, followed by 0.25 mg.kg-1.h-1). Hypoxia was repeated before and after 8-phenyltheophylline administration (19.5 mumol.kg-1, intravenously) in seven rabbits, or before and after vehicle injection in five rabbits (time control).


RESULTS
The PaO2 attained at the end of the hypoxic period was 19(SEM 1) mm Hg [2.5(0.1) kPa]. Before adenosine receptor blockade, arterial pressure increased during hypoxia [14(6)mm Hg after 1 min], then decreased [7.3(8.8) mm Hg below control after 4 min]. Heart rate fell by 38.3(12.1) beats.min-1 in the last 3 min of hypoxia. Vagal negative chronotropic effect increased from -30.3(1.8) beats.min-1 during control to -58.7(4.6) beats.min-1 during the last 5 min of hypoxia, ie, a potentiation of 93.2(9)%. Administration of 8-phenyltheophylline reduced the effects of hypoxia on spontaneous heart rate and vagal bradycardia: heart rate decreased by 14.2(7.8) beats.min-1 and vagal negative chronotropic effect increased from -32.2(2.1) to -39.3(3.7) beats.min-1, ie, a potentiation of 21.5(10)%. Blood pressure showed a stronger increase [19.1(4.4) mm Hg after 2 min], but no decrease. These differences were not seen in the five control rabbits, in which hypoxia was repeated without adenosine receptor blockade.


CONCLUSIONS
These results show that adenosine does play a role in hypoxia induced bradycardia and vagal potentiation.
Laboratorium voor Fysiologie, Vrije Universiteit, Amsterdam, The Netherlands.
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Verlato
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Borgdorff
D000241:Adenosine / Q000502:physiology*; D000758:Anesthesia; D000818:Animals; D003864:Depression, Chemical; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D011817:Rabbits; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects / Q000503:physiopathology*
D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine