Endogenous adenosine enhances vagal negative chronotropic effect during hypoxia in the anaesthetised rabbit.

Abstract

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 mumol.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(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.

• Authors: G Verlato, P Borgdorff
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 24 Issue 7 Pg. 532-9 (Jul 1990) ISSN: 0008-6363 [Print] England
• PMID: 2208206 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Theophylline
• 8-phenyltheophylline
• Adenosine

Topics

• Adenosine (physiology)
• Anesthesia
• Animals
• Depression, Chemical
• Female
• Heart Rate (drug effects)
• Hypoxia (physiopathology)
• Male
• Rabbits
• Theophylline (analogs & derivatives, pharmacology)
• Vagus Nerve (drug effects, physiopathology)