Role of adenosine receptors in the paradoxic bradycardia response of rats to inferior vena cava occlusion during an infusion of isoproterenol.
BACKGROUND
In susceptible humans, vasodepressor reactions are induced by restriction of venous return (upright tilting) and administration of isoproterenol. Because paradoxic bradycardia is a major manifestation of vasodepressor reactions, and allowing for extrapolation between paradoxic bradycardia in rats and vasodepressor reactions, we examined whether adenosine receptors mediate the paradoxic bradycardia reaction.


RESULTS
Paradoxic bradycardia was induced in rats by inferior vena cava occlusion during an isoproterenol infusion. We studied whether dipyridamole, an adenosine transport inhibitor, and aminophylline (nonselective) or DPCPX (selective) A1 antagonists augmented or inhibited paradoxic bradycardia, respectively, during inferior vena cava occlusion. The maximum changes in R-R during 60 seconds of inferior vena cava occlusion were that (1) in control, the rate accelerated (DeltaR-R, -9.7+/-0.8 ms, P<0.001); (2) during isoproterenol (0.8 microg . min-1), paradoxic bradycardia occurred (DeltaR-R, +92.0+/-32.0 ms, P<0.001); (3) during isoproterenol but after dipyridamole, paradoxic bradycardia occurred at a much lower dose of isoproterenol (0.2 microg . min-1), and the magnitude was increased at all doses (at 0.8 microg . min-1 isoproterenol, DeltaR-R, +195.6+/-27.6 ms, P<0.001 versus isoproterenol alone, DeltaR-R, +92.0+/-32 ms); (4) during isoproterenol and dipyridamole, atropine did not block paradoxic bradycardia, but cervical vagotomy inhibited paradoxic bradycardia (DeltaR-R, +5.6+/-1.8 ms, P<0.001 compared with isoproterenol and dipyridamole alone); and (5) during isoproterenol alone, aminophylline or DPCPX blocked paradoxic bradycardia (DeltaR-R, -5.4+/-1.0 ms, and DeltaR-R, -2.6+/-0.5 ms, respectively, each P<0.001 compared with isoproterenol alone).


CONCLUSIONS
The adenosine A1 receptor mediates the paradoxic bradycardia reflex during inferior vena cava occlusion in the face of isoproterenol via vagal afferents.
Waxman
M B
MB
Department of Medicine of the University of Toronto and the Division of Cardiology of the Toronto Hospital, Ontario, Canada.
Asta
J A
JA
D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000209:etiology*; D004176:Dipyridamole / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D014630:Vagus Nerve / Q000502:physiology; D014682:Vena Cava, Inferior / Q000502:physiology*; D014970:Xanthines / Q000494:pharmacology
D018047:Receptors, Purinergic P1; D014970:Xanthines; D000628:Aminophylline; D004176:Dipyridamole; D000255:Adenosine Triphosphate; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D007545:Isoproterenol