ENDOGENOUS ADENOSINE ENHANCES VAGAL NEGATIVE CHRONOTROPIC EFFECT DURING HYPOXIA IN THE ANESTHETIZED RABBIT

Study 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.Design - 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.Experimental material - 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 μmol·kg-1, intravenously) in seven rabbits, or before and after vehicle injection in five rabbits (time control).Measurements and 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(3.7) beats·-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.